Improved prognostication in small (pT1) breast cancers by image cytometry

Summary Feulgen-stained samples from 460 small (pT1) primary breast cancers were investigated by means of an image analysis system. Several DNA, morphometrical and textural parameters were evaluated for each patient, and the prognostic meaning of these parameters was then investigated by the Cox regression analysis. As prognostic criterion a distant recurrence-free survival of five years was considered.All investigated DNA- and morphometrical parameters as well as several textural parameters showed a significant univariate correlation with the clinical course. In a multivariate approach the axillary nodal status was the most important prognostic parameter, followed by a morphometric parameter (anisokaryosis) and two textural parameters (runlength and co-occurrence). None of the DNA histogram derived parameters could add prognostic information in this multivariate approach. By the linear combination of the four selected variables, an individual prognostic factor was calculated. Using this factor the patients could be split into several groups according to their risk for distant metastases. Thus a low risk group of pT1 patients could be identified with a distant recurrence rate of only 2% after 5 years, and also a group of patients with a considerably worse prognosis and a 5-year distant recurrence rate of 53%. In contrast, using the nodal status as single parameter allows the identification of a low risk group of patients (pN0pT1) with a disant recurrence rate of 10.6%. Therefore, morphometrical and textural parameters can provide powerful prognostic information in small breast carcinomas and may allow a better selection of patients for adjuvant therapy.     

The Effect of 3'-Deoxyadenosine N1-Oxide on Growth in Vitro and in vivo on Ehrlich Ascites Tumor and on a Human Squamous Lung Cell Carcinoma Xenograft in Nude Mice

The effect of 3'-deoxyadenosine N¹-oxide (3'-dANO) on Ehrlich ascites tumor and a human squamous lung cell carcinoma was investigated. The 3'-dANO concentration that inhibited the cell growth 50% (IC₅₀) in Ehrlich ascites tumor cells in vitro was 0.15 mM, and the killing efficiency concentration (concentration of the drug that kills all cells) was 1 mM. By simultaneous administration of 3'-dANO and the adenosine deaminase inhibitor erythro-9-(2-hydroxyl-3-nonyl) adenine (EHNA), the IC₅₀ of 3'-dANO was unchanged, but the killing efficiency concentration of 3'-dANO was reduced to 0.3 mM. When mice bearing Ehrlich ascites tumor were treated i.p. with 3'-dANO doses of 200 mg/kg daily for 4 days, the mean increased life span (ILS) was 200%. 3'-dANO in combination with EHNA did not further increase the life span of the tumor-bearing mice. The specific growth delay (SGD) of the Ehrlich tumor and of a human squamous lung cell carcinoma growing subcutaneously in 3'-dANO-treated mice were calculatedfrom Gomperts tumor growth curves. The Ehrlich tumor-bearing mice received 3'-dANO i.p. at doses of 250 mg/kg daily for 4 days, and the nude mice bearing human carcinoma received 3'-dANO i.p. at doses of 225 mg/kg daily for 5 days. The SGD for the investigated tumors were calculated to be 1.0 and 1.1, respectively.     

Treatment of long-term sterility by intra-tubal gamete transfer

It is reported about a first successful program of gamete intra fallopian transfer (GIFT) as a supplement to intrauterine insemination and to in vitro fertilization (IVF). In 29 patients after HMG stimulation of the ovaries and laparoscopic aspiration of follicles recovered oocytes have been introduced together with prepared sperm via a special catheter directly into the ampulla of the oviduct. In 21 patients with different causes of infertility optimal stimulation conditions could be achieved. A pregnancy rate of 41.4% is the result of 29 GIFT events and 3 of them resulted in spontaneous term deliveries (10.3%).     

Immunohistochemical demonstration of the co-expression of vimentin and cytokeratin(s) in the guinea pig cochlea

Summary Using a decalcification procedure for guinea pig petrous bones, we were able to prepare cryostat sections for immunohistochemical studies. A panel of monoclonal antibodies against intermediate filament proteins was then used to show a co-expression of cytokeratin and vimentin in the epithelial cells of the stria vascularis.     

Revision acetabular arthroplasty using a pedestal cup in patients with previous congenital dislocation of the hip - four case reports and review of treatment

Despite extensive acetabular bone defects as found in revisions of total hip arthroplasty for high hip dislocation, the ilium usually still provides secure fixation of the pedestal of the acetabular component. Four cases are presented in which reconstruction was performed using a newly developed, conical, titanium, ribbed shaft socket designed for cementless press-fit into the dorsocranial ilium to obtain primary stability. In each case the pedestal cup allowed restoration of the original centre of rotation. There were no complications. A Harris hip score of 85 points was achieved after an average of 28.5 months. All components were radiologically stable. While the findings demonstrate the short-term efficacy of the procedure, longer follow-ups and a larger number of patients are needed before the durability of this reconstructive technique can be assessed.     

The biological and biomechanical effect of different graft tensioning in anterior cruciate ligament reconstruction: an experimental study

The objective of the present animal experimental study was to determine the effect of initial graft tension (1 N, 7.5 N, 17.5 N) on the biomechanical and histological behavior of the anterior cruciate ligament (ACL) graft using a rabbit model. After 2, 8, and 32 weeks, the femur-ACL-tibia complex was removed, and biomechanical and histomorphometrical studies were performed. The morphometric parameters cellularity, cell nucleus volume, and vascularity increased up to the 8th postoperative week and showed significant differences between the study groups. The values obtained demonstrated that higher pretension had increased the pull-out force and stiffness. However, at 32 weeks postoperatively, the pull-out force was significantly below the values of the normal ACL (40.5% at 1 N, 45.1% at 7.5 N, and 50.8% at 17.5 N). In the present study, it was demonstrated that an intraoperatively selected initial tension of 17.5 N induces histomorphometric changes in the graft, which result in a higher biomechanical loading capacity. The results showed that higher initial graft tension resulted in improved histological and biomechanical parameters. Pathological changes in the graft such as an increased central necrosis rate or cartilage damage due to 'overconstraining' of the knee were not observed at the selected initial tensions.     

Human retinal pigment epithelial cells inhibit proliferation and IL2R expression of activated T cells

The purpose of this study was to characterize the effects of human retinal pigment epithelial (RPE) cells on activated T cells. Activated T cells were cocultured with adult and foetal human RPE cells whereafter apoptosis and proliferation were determined by flow cytometry and (3)H-Thymidine incorporation assay, respectively. T cells and RPE cells were cultured directly together or in a transwell system for determination of the effect of cell contact. The importance of cell surface molecules was examined by application of a panel of blocking antibodies (CD2, CD18, CD40, CD40L, CD54, CD58) in addition to use of TCR negative T cell lines. The expression of IL2R-alpha -beta and -gamma chains of activated T cells was analysed by flow cytometry after incubation of T cells alone or with RPE cells. Human RPE cells were found to inhibit the proliferation of activated T cells by a cell contact-dependent mechanism. The RPE cells inhibitory abilities were not affected by blocking of any of the tested surface molecules. The inhibition of the T cells' proliferation correlates with a decreased expression of IL2R-beta and -gamma chains. The T cells regain their ability to proliferate and increase their IL2R-beta and -gamma chain expression within 24 hr after removal from the coculture. It is concluded that the cultured human adult and foetal RPE cells inhibit the proliferation of activated T cells by a process that does not involve apoptosis. It depends on cell contact but the involved surface molecules were not revealed. The proliferation inhibition correlates with a modulation of the T cells' expression of IL2R, and is reversible.     

Methicillin-resistant Staphylococcus aureus keratitis after excimer laser photorefractive keratectomy1

A 43-year-old woman in good health was admitted to the hospital 3 days after photorefractive keratectomy (PRK) in the left eye with postoperative bandage contact lens application. She had developed a severe keratitis with ulceration and hypopyon. Upon the patient's admission to the hospital, the contact lens was removed. Ofloxacin eyedrops were prescribed 4 times a day. In the hospital, the patient was successfully treated with immediate thermocautery application, followed by full-thickness keratoplasty the next day and intensive systemic and topical antibiotics. Cultures were positive for methicillin-resistant Staphylococcus aureus (MRSA). Severe MRSA keratitis is a rare cause of infection after PRK.     

Outpatient therapy with gemcitabine and docetaxel for gallbladder,biliary, and cholangio-carcinomas

Purpose. The prognosis of patients withbiliary tree carcinomas is very poor. Thediagnosis often occurs at an advancedstage, when curative resection is notpossible. We combined gemcitabine anddocetaxel to optimize the palliativetherapy for patients with gallbladder,biliary, and cholangio-carcinomas on anoutpatient basis. Patients and methods. Patients withhistologically proven biliary treecarcinomas and a WHO performance status<2 received gemcitabine 1000 mg/m²followed by docetaxel 35 mg/m² weekly for 3weeks followed by 1 week of rest. Results. Forty-three patients, 14males/29 females, with an average age of63.3 years (range, 41 to 78) have beenenrolled since 1998; 37 have completedtreatment. So far, 168 cycles (range, 1 to16) have been administered. All 43 patientswere included in the response and toxicityassessments. There are no completeremissions; however, 4 (9.3%) patientsachieved partial remission, 1 (2.3%) had aminimal remission, and 24 (55.8%)reached disease stabilization for a medianperiod of 5.2 months. Fourteen (32.6%)patients progressed. The median overallsurvival rate is currently 11.0 months. Grade 3 hematologic toxicities wereinfrequent, and there were no grade 4hematologic toxicities. Grade 3 leukopeniawas reported in 4 (9.3%) patients, grade 3thrombozytopenia in 1 (2.3%) patient, andgrade 3 anemia in 1 (2.3%) patient.Twenty-eight (65.1%) patients had grade3/4 alopecia, 8 (18.6%) hadnausea/vomiting, and 2 (4.6%) hadmucositis. Conclusion. The combination ofgemcitabine/docetaxel is an effective andwell tolerated therapy for patients withadvanced or metastatic gallbladder,biliary, and cholangio-carcinomas.