2-deoxy-2-[18]fluoro-D-glucose PET/CT (18FDG PET/CT) may not be a viable biomarker in Pompe disease.

BACKGROUND: Pompe disease (PD) is an autosomal recessive, lysosomal storage disease due to a mutation of the acid α-glucosidase (GAA) gene. In adult patients, PD is characterized by slowly progressive limb-girdle and trunk myopathy and restrictive respiratory insufficiency. Enzyme replacement therapy (ERT) is available, improving or stabilizing muscle-function in some and slowing deterioration in other patients. Unfortunately, there is no biomarker available to indicate therapeutic efficacy and/or disease activity. Whole body MRI depicts all skeletal muscles demonstrating foci of atrophic muscles, i.e., late and irreversible pathological changes. Any method indicating the localizations of increased muscle glycogen storage, muscle inflammation and/or degradation could possibly help identifying newly afflicted tissue and may be of prognostic value. We therefore investigated 2-deoxy-2-[18]fluoro-D-glucose (FDG) PET, a biomarker for glucose-metabolism, as a tool to evaluate disease activity and prognosis in PD. METHODS: In a pilot study, we investigated four patients by FDG dynamic PET/CT while on ERT. One patient had FDG-PET/CT twice, before and after 12 months on ERT. Dynamic FDG-PET/CT quantifies the metabolic rate of glucose utilisation in mg/ml/min. MRI was performed in parallel with pelvic and thigh muscles semi-quantitatively scored for atrophy and disease-activity. RESULTS: None of the muscles analysed showed a focally increased FDG-uptake. Thus, quantification of muscle glucose metabolism could not be calculated. However, increased FDG-uptake, i.e., increased glucose utilisation, was observed in the respiratory muscles of one patient with severe, restrictive respiratory failure. In contrast, specific MRI sequences showed oedematous as well as atrophic muscle areas in PD. CONCLUSIONS: Our pilot study demonstrates that FDG-uptake does not correlate with glycogen storage in vivo. In contrast, MRI is an excellent tool to demonstrate the extent of muscle involvement. Specific MRI sequences may even demonstrate early changes possibly allowing prognostic predictions or localization of early stages of PD.

[Neuroendocrine tumors of the larynx]. / Neuroendokrine Tumoren des Larynx.

BACKGROUND: The location of neuroendocrine tumors in the larynx (NETL) is atypical and relatively rare. It has become possible to determine increasing numbers of these tumors in recent years owing to improvements in immunohistological methods. Extensive recommendations were made with regard to diagnostics and treatment by the "European Neuroendocrine Tumor Group" in 2004. These recommendations relate mainly to the very much more frequent gastroenteropancreatic neuroendocrine tumors and cannot be applied directly to NET of the larynx. This is why precise scientific investigations of NETL and publications of new cases are important. METHODS: Retrospective review of all laryngeal malignancies treated from 1994 to 2004 revealed a NETL in three of about 1000 patients. These patients were evaluated with regard to clinical symptoms, tumor locations, immunohistological findings and the clinical courses. RESULTS: Evaluation of the patients (incidence 0.23%: average age 58 years: female to male 1:2) revealed a poorly differentiated neuroendocrine carcinoma in two patients and a moderately differentiated neuroendocrine carcinoma in one patient. After surgical treatment and radiochemotherapy, the patients with a poorly differentiated carcinoma survived for seven and 17 months respectively and the patient with a moderately differentiated carcinoma survived for 30 months. The patients investigated showed findings consistent with those of previously published cases with regard to the parameters investigated. CONCLUSIONS: NETL require more extensive staging investigations and a specific treatment adapted to the subtyping. Treatment at specialized centers with publication of individual cases is desirable to extend and deepen knowledge.

Collagens serve as an extracellular store of bioactive interleukin 2.

The binding of certain growth factors and cytokines to components of the extracellular matrix can regulate their local availability and modulate their biological activities. We show that interleukin 2 (IL-2), an important stimulator of T cell growth, preferentially binds to collagen types I, III, and VI and to a lesser degree to collagen types II, IV, and V, immobilized on polystyrene or nitrocellulose. These interactions are inhibited by denatured, single collagen chains or a subset of their cyanogen bromide peptides in a dose-dependent manner. Cross-inhibition experiments and ligand blotting of collagen-derived peptides point to a limited set of collagenous consensus sequences mediating the binding of IL-2. This interaction is saturable, with dissociation constants of approximately 10(-)(8) m, and estimated molar ratios of 4-6 molecules of IL-2 bound to one molecule of triple helical collagen. Furthermore, collagen-bound IL-2 stimulates proliferation of mouse lymphocytes. We conclude that its specific binding to the abundant interstitial collagens leads to a spatial pattern of bioavailable IL-2 which is dictated by the local organization of the collagenous extracellular matrix. This interaction may contribute to the particular phenotype of stromal lymphocytes and could be exploited for devising collagenous peptide analogues that modulate IL-2 bioactivity.