Plaque-forming cells in human cord blood: studies on T and B cell function

Fewer plaque-forming cells (PFC) were found in the cord blood than in adult blood. B cells of newborns seem to be functionally mature. T cells of newborns provide enough help but exert increased suppressor activity.     

Changes in Mcl-1 expression in rectal cancer in relation to neo-adjuvant radiotherapy

BACKGROUND: Expression of the antiapoptotic protein myeloid cell leukemia-1 (Mcl-1) may be disordered in malignancies of the rectum. High levels of Mcl-1 may correlate with unfavourable clinical outcome. AIM OF THE STUDY: The aim of the study was to determine the biologic significance and the prognostic value of the protein Mcl-1 in a group of patients with rectal cancer using immunohistochemical staining in archival specimens. PATIENTS AND METHODS: Expression of the Bcl-2 family member Mcl-1 was determined in 23 rectal malignancies. Half of the patients with rectal cancer were treated with preoperative short-term radiation therapy of 25 Gy followed by radical surgery; the other patients were treated just with radical surgery. Differences in Mcl-1 expression between irradiated and non-irradiated rectal cancer cells were analysed immunohistochemically, and Mcl-1 expression was correlated with overall survival. Induction of Mcl-1 expression by irradiation versus control in colorectal cancer cells was detected using Western blot. RESULTS: Mcl-1 was expressed at high levels in 35% of all specimens. Significantly stronger expression was detected in specimens of irradiated rectal cancer compared with non-irradiated tissues (p-value: 0.005). No association was seen between marker expression patterns and clinicopathological data of the respective patients. CONCLUSION: Our findings indicate that irradiated rectal cancer produces significantly higher levels of the antiapoptotic protein Mcl-1 than non-irradiated rectal carcinoma. The data also suggest that the high level of Mcl-1 was induced by the radiotherapy. As Mcl-1 is an antiapoptotic regulator, its over-expression in irradiated rectal cancer could constitute a detrimental development antagonizing the potential benefit of adjuvant radiotherapy. Further evaluation of the correlation between Mcl-1 expression and overall survival seems warranted.     

Zoledronate in a patient with pamidronate refractory hypercalcemia syndrome

Hypercalcemia of malignancy remains a common metabolic complication of advanced cancer often resulting in considerable morbidity and diminishing life quality in the later stages of disease. Bisphosphonates, especially zoledronic acid, are potent inhibitors of bone resorption and are the most effective therapy for hypercalcemia of malignancy. We report on the course of disease in a 51-year-old woman who presented with metastatic breast cancer that had relapsed to the liver. The patient suffered from a pamidronate-refractory paraneoplastic hypercalcemia, which caused a confused mental status and compromised her already severely limited life quality. Only with the introduction of zoledronate could the patients hypercalcemia be normalized with consecutive regain of an acceptable life quality.     

Focal and diffuse forms of congenital hyperinsulinism: The keys for differential diagnosis

Congenital hyperinsulinism is clinically characterized by an inappropriate insulin secretion resulting in recurrent severe hypoglycemia. Nesidioblastosis, the proliferation of islets cells budding off from pancreatic ducts, has been considered for years as the histological lesion responsible for the syndrome. In our morphological studies, we demonstrated that nesidioblastosis is not specific for the disease, which is actually not a single entity. Indeed, we recognized the existence of two different forms—a diffuse form and a focal form—and demonstrated that they can be differentiated on the basis of morphological criteria, even on frozen sections during surgery. This histological distinction directs the therapeutic approach because the patients suffering from the focal form of the syndrome can be completely cured by a very limited pancreatectomy. Molecular findings confirmed the reliability of this histological distinction, showing a specific genetic background for each form.     

Current options in prosthetic vascular graft infection: comparative analysis of 63 consecutive cases

Purpose The study was conducted to compare the results of two different techniques of vascular reconstruction in patients after the removal of infected vascular prostheses.Methods Sixty-three patients with vascular prostheses infections underwent treatment. Either the infected fragments or the entire prosthesis was removed in all of the patients. Extra-anatomical grafts were implanted in 19 cases. Cryopreserved allogenic arterial grafts were applied for reconstruction in 44 patients.Results In a 19-patient group with extra-anatomical grafts, two patients died (10.5%). In seven patients (36.8%) relapse symptoms of infection appeared. Primary and secondary patencies of the grafts after 3 years were 31.6% and 52.6% respectively. In a group of 44 patients with allogenic grafts no recurrence of infection was observed. Six patients died (13.6%). Primary and secondary patencies after 3 years were 63.6% and 81.8% respectively.Conclusions The results reveal the benefits of the allogenic arterial grafts in revascularization in patients with major vascular prostheses infections. The differences in secondary patencies of the implanted allogenic grafts indicate the necessity of an early selection of patients for the complete removal of the infected prosthesis, during a time when patients are in general good health.     

Web-based, virtual course units as a didactic concept for medical teaching

The objective was to develop a web-based, virtual series of lectures for evidence-based, standardized knowledge transfer independent of location and time with possibilities for interactive participation and a concluding web-based online examination. Within the framework of a research project, specific Intranet and Internet capable course modules were developed together with a concluding examination. The concept of integrating digital and analogue course units supported by sound was based on FlashCam (Nexus Concepts), Flash MX (Macromedia), HTML and JavaScript. A Web server/SGI Indigo Unix server was used as a platform by the course provider. A variety of independent formats (swf, avi, mpeg, DivX, etc.) were integrated in the individual swf modules. An online examination was developed to monitor the learning effect. The examination papers are automatically forwarded by email after completion. The results are also returned to the user automatically after they have been processed by a key program and an evaluation program. The system requirements for the user PC have deliberately been kept low (Internet Explorer 5.0, Flash-Player 6, 56 kbit/s modem, 200 MHz PC). Navigation is intuitive. Users were provided with a technical online introduction and a FAQ list. Eighty-two students of dentistry in their 3rd to 5th years of study completed a questionnaire to assess the course content and the user friendliness (SPSS V11) with grades 1 to 6 (1 = 'excellent' and 6 = 'unsatisfactory'). The course units can be viewed under the URL: http://giga.rrze.uni-erlangen.de/movies/MKG/trailer and URL: http://giga.rrze.uni-erlangen.de/movies/MKG/demo/index. Some 89% of the students gave grades 1 (excellent) and 2 (good) for accessibility independent of time and 83% for access independent of location. Grades 1 and 2 were allocated for an objectivization of the knowledge transfer by 67% of the students and for the use of video sequences for demonstrating surgical techniques by 91% of the students. The course units were used as an optional method of studying by 87% of the students; 76% of the students made use of this facility from home; 83% of the students used Internet Explorer as a browser; 60% used online streaming and 35% downloading as the preferred method for data transfer. The course units contribute to an evidence-based objectivization of multimedia knowledge transfer independent of time and location. Online examinations permit automatic monitoring and evaluation of the learning effect. The modular structure permits easy updating of course contents. Hyperlinks with literature sources facilitate study.     

Neoplastic stem cells: a novel therapeutic target in clinical oncology

Cancer is among the leading causes of morbidity and mortality in the Western world. Despite recent advances, most therapeutic approaches fail to eradicate the entire neoplastic clone. The remaining cells often develop metastasis and/or recurrences and therefore may represent attractive targets of therapy. A new exciting concept in this regard suggests that each neoplasm represents a heterogeneous population of cells that pertain to long-term tumor growth both in vivo in the natural host and in experimental animals. This concept postulates the existence of small fractions of 'tumor stem cells' that exhibit a capacity for self-renewal and unlimited growth and therefore are distinct from their progeny. Based on these hypotheses, the targeting of neoplastic stem cells is considered indispensable for eradication of the entire clone and for the development of curative treatment approaches. However, tumor stem cells often may be quiescent cells and may express a different profile of targets compared with 'more mature' tumor cells. Therefore, current efforts have attempted to characterize target expression profiles in cancer stem cells in various malignancies. In the this review, the authors have provided a brief summary of the current knowledge of neoplastic stem cells and the application of respective concepts in translational oncology with the ultimate objective of improving anticancer therapy.