Pretreatment of lipopolysaccharide (LPS)-responder C57BVlOScSn mice with killed Propionibacterium acnes enhanced tumor necrosis factor alpha (TNF-a) production and lethality in response to a subsequent challenge with LPS. Sensitization to LPS increased with time of pretreatment and reached its maximum after 7 days. Sensitization was paralleled by gamma interferon (IFN-y) production that was detectable from day 3 onward. In contrast, a similar P. acnes pretreatment of LPS-nonresponder C57BL/lOScCr mice had no apparent effect on their high resistance to LPS. Challenge with LPS at any time during the 7-day period after P. acnes treatment led to no detectable TNF-ax formation and caused no lethal effects. The absence of sensitization in C57BL/lOScCr mice was paralleled by an absence of IFN-y production. Administration of monoclonal IFN-y antibodies in C57BLIlOScSn mice up to day 3 ofP. acnes treatment completely inhibited the overproduction of TNF-a by LPS. Anti-IFN-y administered later than day 3 had only a partial, although significant, inhibitory effect. Injection of appropriate amounts of anti-IFN-y also abolished the development of hypersensitivity to the lethal action of LPS. The effect of exogenously administered IFN-y on LPS sensitivity (e.g., TNF-ct production, lethal effects) was studied in LPS-responder and nonresponder mice. Administration of murine recombinant IFN-y increased the sensitivity of C57BLJlOScSn mice to LPS and established LPS responsiveness in LPS-nonresponder C57BL/lOScCr and C3H/HeJ mice. The data provide evidence that IFN-y mediates the sensitization towards LPS induced by P. acnes. Bacterial lipopolysaccharides (LPS, endotoxins) are causative agents of a number of pathophysiological reactions seen during infection with gram-negative pathogens. Many of these reactions are elicited by purified LPS in experimental animals (for a review, see reference 30). The interaction of LPS with macrophages and the subsequent formation of endogenous mediators represent essential early steps in the development of LPS lethal toxicity (16, 18, 31, 44). Tumor necrosis factor alpha (TNF-a), a macrophage-derived cytokine inducible by LPS (5, 45), has been recognized as a principal mediator of endotoxin shock. Injection of mice with exogenous TNF-a leads to pathophysiological reactions similar to those seen after LPS administration (36, 38, 60). Antibodies against TNF-a were shown in different experimental models to protect mice from LPS lethality (2, 17, 20, 61). Susceptibility to LPS of different mouse strains is genetically determined. LPS responsiveness is controlled by a gene locus identified on mouse chromosome 4. It occurs in two allelic forms, lps' for normal and lpsd for defective responsiveness (51). To date, three lpsd mouse strains, C3H/HeJ, C57BL10/ScCr (Cr), and C57BL/1OScSN (Sn), are known (10, 51, 56, 62). Mice belonging to these strains are highly resistant to all known LPS effects, including its

While breast feeding should be promoted for children at risk for atopy, mothers can be encouraged to stay on normal diet during pregnancy and the breast feeding period.

The HEC regimen is a promising treatment option for patients with HER2-positive MBC. The lower incidence of DLC with HEC, compared with the historic incidence associated with trastuzumab plus doxorubicin, supports further evaluation of the regimen, especially in adjuvant or neoadjuvant settings.

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Aim: To investigate the role of DNA aneuploidy, particularly in patients with node negative breast cancer, in order to identify the different risk profiles within the pool of heterogeneous breast cancers. Methods: Imprint smears from 370 breast carcinomas were Feulgen-stained and measured by DNA image analysis. DNA aneuploidy was graded by the amount of aneuploid cells (DNA content .5c) and highly aneuploid cells (DNA content .9c) in a breast tumour population. These results were correlated to the clinical long-term follow-up. A statistical cut-off value of .10 aneuploid cells (.5c) and of .1 highly aneuploid cell (.9c) was evaluated as significant for disease-free survival (DFS) and overall survival (OS). Results: Subgroups among patients with breast cancer with aneuploid cells below the cut-off value showed a significantly longer DFS and OS than those with aneuploid cells above this value. Patients with node negative breast cancer with .10 aneuploid cells (.5c) and .1 highly aneuploid cell (.9c) showed an unfavourable prognosis similar to patients with node positive breast cancer with ,10 aneuploid cells (.5c) and ,1 highly aneuploid tumour cell (.9c) in DFS and OS. Conclusion: Nuclear DNA content, as an objective marker of tumour aggressiveness, provides prognostic information in patients with both node negative and node positive breast cancer. Based on DNA aneuploidy, the clinically inhomogeneous group of patients with node negative breast cancer can be stratified into low-risk and high-risk subgroups. Therefore, DNA ploidy analysis may identify high-risk patients with lymph node negative breast cancer who might benefit from additional adjuvant therapy. B reast cancer is the most common malignant neoplasm in women and has an unpredictable clinical course.

The aim of this survey was to analyse the standard of care in diagnostic, surgery, chemotherapy and aftercare management for patients with borderline tumours of the ovary (BOTs) in Germany. A structured questionnaire comprising different dimensions was sent to all 1114 gynaecological departments. The questionnaire could be returned anonymously. The overall response rate was 29.0% (323 departments). Most departments were on secondary care (71.8%), tertiary care (23.2%) or university hospital (5.0%) level. Most clinicians performed not more than five BOT operations (89.2%) per year. Most departments (93.2%) used in addition to classical bimanual examination and vaginal ultrasound, tumour marker CA-125 detection, CT scan, MRI or PET-CT techniques. Departments in university and tertiary care hospitals performed more often a fresh frozen section (87 vs 64%). In young women, clinicians performed much seldom unilateral salpingo-oophorectomy (92%) and only in 53% biopsies of the contralateral ovary. Generally, biopsies of the contralateral ovary were performed in 4 -53% of the patients. Chemotherapy was mostly favoured in 'high-risk' patients with tumour residual, microinvasion or invasive implants. Thus, a high grade of insecurity in diagnostic and therapy of BOT exists in some gynaecological departments and underlines the need for more educational and study activities.

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We evaluated the diagnostic reliability of cervical examination using digital colposcopy compared with conventional binocular colposcopy. A total of 315 patients were examined and diagnosed by a colposcopist on-site. During the colposcopic examination, digital camera images were stored on a PC (median five pictures per patient). A second physician, experienced in colposcopy, re-evaluated the initial diagnostic findings using the stored digital images. The primary and secondary findings in each patient were categorized according to the Rome classification system. There was agreement between the primary and secondary examiners in 69% of cases (kappa=0.60). There was no systematic bias in terms of under- or over-rating. The proportion of non-assessable colposcopic examinations was 9%. Digital colposcopy was reliable and provided advantages in terms of a better follow-up examination and internal quality control of the diagnosis. The pilot study suggests that telecolposcopy may provide better training and further education for physicians and students, and may also improve the diagnostic possibilities in gynaecology.