Mycobacterium avium infection in BALB/c and SCID mice.

BALB/c and severe combined immunodeficient (SCID) mice were inoculated intraperitoneally with Mycobacterium avium and the numbers of cfu were monitored for 70 days in spleen, liver, lung, kidney, brain and peritoneum. While BALB/c mice formed typical granulomas and controlled bacterial growth in organs, a delay in development of lesions and a modest containment of infection were observed in SCID mice. In the spleen of BALB/c mice, in which bacterial growth was contained, macrophages (Mo) and natural killer (NK) cell numbers increased > or = 4.2 times and T- and B-cell numbers increased > or = 1.8 times after 42 days of infection; conversely, a low recruitment of mononuclear cells was observed in the spleen of SCID mice, where M. avium proliferated efficiently. Unlike visceral organs, a pronounced decrease in the number of cfu was observed in the peritoneum of BALB/c mice, concomitantly with a > or = 31.7-fold increase in Mo and NK cells and a > or = 9.1-fold increase in T and B cells. In the peritoneum of SCID mice only a bacteriostatic effect was observed despite a > or = 56.7-fold increase in Mo and NK cells and a > or = 22.3-fold increase in T and B cells. These results suggest that while an intact immune response can efficiently control M. avium infection in the spleen and peritoneum of BALB/c mice, cells of the innate immune system such as Mo and NK cells play a role in the containment of bacterial growth in the peritoneum, but not spleen, of SCID mice.     

Compliance and diagnostic efficacy of mini-hysteroscopy versus traditional hysteroscopy in infertility investigation

Objective

The aim of this study was to compare traditional hysteroscopy with mini-hysteroscopy in terms of compliance, side effects and diagnostic efficacy.

Study design

We prospectively considered 950 female candidates for an IVF programme. All women underwent outpatient hysteroscopy; in 602 cases (Group A) a mini-hysteroscope was employed; in 348 women (Group B) a 5-mm hysteroscope was adopted.

Results

Cavity findings were similar in both groups. Endometrial polyps and uterine septum seem to be more frequent in our infertile patients than in the general population. No significant differences in terms of side effects were found between the groups. Mean visual analogue pain scale score was significantly lower in the patients of Group A than in those of Group B (p < 0.001).

Conclusions

Office mini-hysteroscopy is a very effective diagnostic tool in an infertility work-up and is more widely accepted than traditional hysteroscopy. Routine use of the technique should be considered.     

Heat-shock protein expression on the membrane of T cells undergoing apoptosis.

Heat-shock proteins (hsp) represent a highly conserved family of proteins, normally localized in the cytoplasm and nucleus, whose expression is induced in situations involving cell stress. This paper reports the unusual translocation of hsp to the cell membrane of T cells undergoing apoptosis. We observed that glucocorticosteroid-induced thymocyte death is associated to the surface expression of hsp 60 and hsp 70 in a discrete fraction of apoptotic cells. hsp surface expression is closely related to a thymic subset of immature CD3low/- T cells. The expression of surface hsp 60 appears early after treatment with dexamethasone (3 hr) whereas the membrane expression of hsp 70 follows different kinetics and peaks later. Morphological analysis of the hsp+ apoptotic cells suggest that this subset represents late-stage apoptotic cells at their minimal volume before fragmentation into apoptotic bodies. Membrane expression of hsp is also associated with apoptosis in peripheral blood mononuclear cells from AIDS patients cultured in vitro. Altogether, we show that a discrete fraction of cells undergoing apoptosis expresses membrane hsp 60 and hsp 70, supporting the hypothesis that apoptosis causes a radical alteration in the expression of cell surface molecules. Surface hsp expressed during apoptosis may constitute a novel immune-context able to generate packages of self- and exogenous antigens, originating from degradation of altered cells.     

Steroid hormone receptor levels and adjuvant tamoxifen in early breast cancer

Summary Ten year disease-free survival (DFS) results of the Naples randomized trial of adjuvant tamoxifen (TM), 30 mg per day for 2 years versus no therapy according to receptor levels, are reported. From Feb. 1, 1978, through Dec. 31, 1983, 308 pre- and postmenopausal patients with early breast cancer entered the trial. Estrogen receptor (ER) data were available on 239 (77.6%) patients, progesterone receptor (PgR) data on 194 (63.0%), and both receptor data on 181 (58.8%).ER and PgR were assayed by dextran-coated charcoal technique in a single laboratory. The effect of adjuvant TM was significantly related to ER and PgR concentration of the primary tumor. The greatest TM benefit on DFS was evident in patients with the highest levels of receptors. The interaction between the treatment effect and receptor concentration was found whether ER and PgR were considered separately or together. Address for reprints: A. Raffaele Bianco, Division of Medical Oncology, University of Naples Medical School II, via S. Pansini, 5-80131 Naples, Italy     

Expression of biomarkers modulating prostate cancer progression: implications in the treatment of the disease

OBJECTIVES: To determine whether COX-2, bcl-2 and neoangiogenesis are related to human prostate cancer relapse after definitive surgical treatment and progression toward androgen independence and to evaluate the association between the patterns of these tumoral biomarkers and other standard clinico-pathological parameters (such as Gleason score, PSA, TNM stage). MATERIALS AND METHODS: We retrospectively analyzed the records on 126 prostate cancer samples from patients treated at our University Hospital from 1995 to 2002. The 72 patients with clinically localized disease (group 1) had undergone radical prostatectomy. Another 54 patients (group 2) had metastatic androgen-independent disease. Archived material relating to the subjects was then immunostained for bcl-2, COX-2 and CD-31, using an anti-bcl-2 monoclonal primary antibody, an anti-COX-2 polyclonal rabbit antibody and an anti-CD-31 monoclonal mouse antibody to evaluate neoangiogenesis (MVD, microvessel density). RESULTS: We found that bcl-2, COX-2 and MVD expression increased from group 1 to group 2. The intergroup difference was significant only for high MVD (P < 0.05). On the other hand, high MVD, high bcl-2 and high COX-2 expression was correlated with a higher PSA level (P < 0.01), whereas only a high MVD was also related with Gleason score (P < 0.05). We used univariate analysis to evaluate the prognostic impact of biologic and clinico-pathologic parameters on the disease-free-survival of 72 patients treated by radical prostatectomy. A total of 30 patients (41.6%) experienced biochemical relapse; bcl-2, COX-2 and MVD significantly correlated with disease relapse in these patients. In fact, we observed disease relapse in 24/45 (53%) with high bcl-2 expression, in 15/21 (71%) with a high MVD count and finally, in 30/58 (52%) with high COX-2 expression. Finally, PSA value and Gleason score were the only two biologic markers significantly associated to disease relapse in a multivariate analysis. CONCLUSIONS: Our results strongly support a role for bcl-2, COX-2 and angiogenesis in the development and progression of prostate cancer. Of course, we are aware of the small sample size considered in our study. Further investigations would better clarify the prognostic and therapeutic implications of these findings.     

Role of chemotherapy in hormone-refractory prostate cancer. Old issues,recent advances and new perspectives

Prostate cancer that grows despite castrate levels of testosterone and that no longer responds to any form of hormonal manipulation and for which nonhormonal approaches are required, can be precisely defined as hormone-refractory prostate cancer (HRPC). Until recently, there has been no standard chemotherapeutic approach for HRPC. In this article recent advances in the treatment of HRPC using chemotherapeutic regimens are critically reviewed. We performed a MEDLINE search of the published reports from 1995 to 2002 including chemotherapy in the treatment of HRPC. We critically reviewed a total of 84 clinical trials, of which only 6 were phase III trials, most of the studies being phase II trials. Various chemotherapeutic agents have been used. To date, the major benefits of chemotherapy in the treatment of HRPC are palliative in nature, in terms of reduction of pain and use of analgesics and improvement of performance status, as followed in the most recent trials. There is a promising activity of new drug combinations, such as vinca alkaloids and taxanes in association with estramustine. Mitoxantrone, although with a limited activity, has been shown to provide improvement in pain and quality of life for the patients. Several studies suffer from methodological deficits, such as small number of patients, heterogeneity of enrolled groups or no definitive response criteria. Further phase III studies are necessary to better evaluate the efficacy of the different regimens.     

Induction of labor in missed abortion, fetal death and vesicular mole, using PGF2 alpha by extra-amniotic intracavitary administration

It has been known for years that prostaglandins can be used to bring on labor. The authors experienced with alpha PGF2 by extraamiotic, intracavitary infusion. The group of 23 patients included 20 cases of incomplete abortion in the second trimester, 9 cases of intrauterine fetal death in the third trimester, and 1 case of vesicular mole. This method proved 82.6% successful: in 56.9% of cases the product of conception was expelled within 12 hours; in 26.5% of cases within 24 hours. Only in 4 cases, 17.4%, this method proved unsuccessful; oxytocin was used in 3 of these 4 cases. Hypertonia was evident immediately after infusion; uterine contractions, measured and registered with a tocograph, were frequent and increasingly intense. Nausea, vomiting and diarrhea were observed in 26.5% of cases; 1 patient had facial flush. These side effects were probably due to the low absorption of the drug into the circulation. Results obtained confirm others described in the literature on the subject.