Circulating endothelial cells in malignant disease

Cancer is a disease largely dependent on neoangiogenesis. Cancer neoangiogenesis is often disordered and abnormal, with evidence of coexisting vascular endothelial dysfunction. A novel method of assessing vascular endothelial function in cancer is via the quantification of circulating endothelial cells (CEC). Unusual in healthy individuals, their presence in elevated numbers often indicates substantial vascular endothelial perturbation. Another interesting cell type is the endothelial progenitor cell (EPC), whose numbers increase in the presence of vascular damage. Recent research suggests that EPCs have an important role in tumor vasculogenesis. Another marker being investigated in the context of vascular dysfunction and coagulopathy is the endothelial microparticle (EMP). Thus, CECs, EPCs and EMPs may represent potentially novel methods for evaluating the vascular status of cancer patients. This review will summarize the current position of CECs, EPCs and EMPs in cell biology terms, with particular emphasis on their relationship to malignant disease.     

Gastroenteritis outbreak in British troops, Iraq

Gastroenteritis affected many British military personnel during the war in Iraq. In the first month, 1,340 cases were seen; 73% of patients required hospital admission and 36% were hospital staff. In a survey of 500 hospital staff, 76% reported gastroenteritis, which was more likely in clinical workers. Investigations showed only caliciviruses.     

Expression of fibronectin and TGF-ß1 mRNA and protein suggest altered regulation of extracellular matrix in degenerated disc tissue

We studied the distribution of fibronectin (a marker for active reparative connective tissue processes) and TGF-1 (a cytokine controlling the connective tissue metabolism) in intervertebral disc tissue from individuals of different age and various histomorphological evidence for tissue degeneration. The protein deposition was determined by immunohistochemistry on 30 complete cross-sections of lumbar spine obtained at autopsy (0–86 years) and 12 surgically removed disc samples. The mRNA expression was detected by non-radioactive in situ hybridization in the surgical material. All control experiments (blank and isotype controls in immunohistochemistry/sense controls in in situ hybridization) were negative. Immunohistochemically, we detected enhanced staining for fibronectin in both nuclear and anular tissues in areas with histological signs of mild-to-severe tissue degeneration (e.g., cleft formation and cell clustering) beginning with 16 years of age. Anular tissue showed less fibronectin staining than did nuclear areas. Fibronectin mRNA was detected mainly in nuclear cells by in situ hybridization corresponding to the protein staining indicating de novo synthesis. In parallel, TGF-1 was expressed by nuclear and occasional anular cells spatially associated with the fibronectin synthesizing cells. This was seen by both immunohistochemistry and in situ hybridization. This preliminary study provides evidence for a significant ongoing rearrangement of the extracellular matrix during disc degeneration, as monitored by enhanced fibronectin deposition that is produced by local disc cells. These cells also synthesize TGF-1, as shown by protein and mRNA expression. Since it is known that TGF-1 induces matrix alterations (by auto and paracrine stimulation of matrix synthesis), these observations suggest that the recently described disturbance of the matrix during disc degeneration may be induced by TGF-. This may offer new approaches to interfere with disc matrix alterations.     

Klinische Prüfungen mit Kindern aus der Sicht eines Zentrums

The 12th AMG amendment and the EU Directive 2001/20/EC set down clear legal guidelines on clinical studies of drug products in children. As a consequence there are new prospects for an increasing involvement of the pharmaceutical industry in developing drugs for use in children. BfArM has acted on this development by setting up a committee of experts on drug approval for use in children-similar to committees at the EMEA and FDA working on the same issue. Another useful step consists in the strengthening of pharmaco-vigilance measures. Treatment standards have been developed on the basis of the research instrument "clinical therapy optimization studies", frequently conducted as co-operative national or international studies joining many trial sites, and may definitely benefit from the new requirements. Clearly defined terms and regulations, such as "sponsor responsibility", "trial approval", "investigational medical product", "insurance", and "monitoring" describe problems that can or at times cannot be solved by such research groups. The sponsor's responsibilities in an international trial e. g. cannot usually be shouldered by a single scientist or treatment center. When in the future practically every single research question on drug treatment is governed by those regulations, costs will soar and fewer questions will be asked in clinical studies. So far, the AMG amendment has not given an assessment of benefit and risk regarding treatment quality and drug safety in children. Such an assessment depends on the willingness of all concerned to explore the scope of the legal regulations in order to let children participate in scientific progress where it is needed and where it makes sense.