Imaging of activated microglia with PET and [11C]PK 11195 in corticobasal degeneration.

Positron emission tomography (PET) using [(11)C]PK 11195, a ligand for peripheral benzodiazepine receptor binding sites, offers the opportunity to image activated microglia in vivo. This tool may therefore be used to display the occurrence of microglial activation in the course of neurodegeneration. A patient with the clinical diagnosis of corticobasal degeneration (CBD) and left-sided symptoms was studied using fluorodeoxyglucose (FDG) and [(11)C]PK 11195 PET. We found a marked right hemispheric hypometabolism and asymmetric microglial activation in corresponding areas of the basal ganglia and right temporal and parietal cortex. [(11)C]PK 11195 PET suggests involvement of microglial activation in the pathogenesis of CBD.     

Cell surface display of rat invariant gamma chain: detection by monoclonal antibodies directed against a C-terminal gamma chain segment.

A series of 14 monoclonal antibodies (mAb) directed against the C-terminal part of the rat invariant gamma chain (amino acid 142-216) was generated using distinct fusion proteins that contain this gamma segment for immunization and hybridoma screening. Additional fusion protein were prepared carrying discrete regions of the gamma chain. Employing these reagents confirmed that the obtained mAb do indeed recognize the C-terminal portion of the invariant chain, as demonstrated by Western blot analysis. All mAb established recognize epitopes present on the native gamma chain, as revealed by immunoprecipitation analysis using nonionic detergent extracts of metabolically labeled Lewis rat splenocytes combined with two-dimensional gel electrophoresis. However, while the majority of the gamma chain-specific mAb precipitated gamma chain-containing polypeptide chain complexes in which immature, sialic acid-deficient and mature, terminally sialylated forms of the gamma chain were predominantly represented, a fraction of the antibodies preferentially precipitated the immature gamma forms. Cell surface binding of these two groups of mAb correlated with the immunoprecipitation data in that the former group of antibodies did bind to intact Lewis rat spleen cells, while essentially no binding was observed with the antibodies of the latter group. Double-fluorescence staining with the class II-specific fluorescein isothiocyanate-conjugated mAb OX3 and OX6, respectively, as well as a representative gamma chain-specific mAb visualized with phycoerythrin-coupled secondary antibody shows coexpression of class II determinants and the invariant chain at the cell surface.     

Experience with carbon-11 choline positron emission tomography in prostate carcinoma

We investigated the potential of carbon-11 choline positron emission tomography (PET) for the detection of lymph node and bone metastases in prostate cancer. A total of 23 patients were studied (known metastases: 8; suspicion of metastases: 3; primary staging: 12). Whole-body PET imaging was performed 5 min after injection of the tracer and completed within 1 h. Focally increased tracer uptake in bone or abdominal lymph node regions was interpreted as representing tumour involvement. All known bone and lymph node metastases could be recognized by [11C]choline PET. One out of ten negative scans for primary staging was false-negative (lymph node <1 cm) and one out of two positive scans was false-positive with regard to lymph node involvement (focal bowel activity). It is concluded that [11C]choline PET is a promising new tool for the primary staging of prostate cancer, with lymph node and bone metastases demonstrating high tracer uptake. Therapeutic management could be influenced by these results in that the technique may permit avoidance of surgical lymph node exploration.     

Risk Factors for Acquisition and Loss of Clostridium difficile Colonization in Hospitalized Patients

Asymptomatic colonization may contribute to Clostridium difficile transmission. Few data identify which patients are at risk for colonization. We performed a prospective cohort study of C. difficile colonization and risk factors for C. difficile acquisition and loss in hospitalized patients. Patients admitted to medical or surgical wards at a tertiary care hospital were enrolled; interviews and chart review were performed to determine patient demographics, C. difficile infection (CDI) history, medications, and health care exposures. Stool samples/rectal swabs were collected at enrollment and discharge; stool samples from clinical laboratory tests were also included. Samples were cultured for C. difficile, and the isolates were tested for toxins A and B and ribotyped. Chi-square tests and univariate logistic regression were used for the analyses. Two hundred thirty-five patients were enrolled. Of the patients, 21% were colonized with C. difficile (toxigenic and nontoxigenic) at admission and 24% at discharge. Ribotype 027 accounted for 6% of the strains at admission and 12% at discharge. Of the patients colonized at admission, 78% were also colonized at discharge. Cephalosporin use was associated with C. difficile acquisition (47% of patients who acquired C. difficile versus 25% of patients who did not; P = 0.03). β-lactam–β-lactamase inhibitor combinations were associated with a loss of C. difficile colonization (36% of patients who lost C. difficile colonization versus 8% of patients colonized at both admission and discharge; P = 0.04), as was metronidazole (27% versus 3%; P = 0.03). Antibiotic use affects the epidemiology of asymptomatic C. difficile colonization, including acquisition and loss, and it requires additional study.     

Choosing the optimal fit function: comparison of the Akaike information criterion and the F-test

In many circumstances of data fitting one has to choose the optimal fitting function or model among several alternatives. Criteria or tests on which this decision is based are necessary and have to be well selected. In this preliminary analysis the application of the corrected Akaike information criterion is demonstrated considering the example of determining pharmacokinetic parameters for the blood serum time activity curves of 111In-labeled anti-CD66 antibody. Another model selection criterion, the F-test, is used for comparison. For the investigated data the corrected Akaike information criterion has proved to be an effective and efficient approach, applicable to nested and non-nested models.     

Primary staging of lymphomas: cost-effectiveness of FDG-PET versus computed tomography

The objective of this study was to measure the incremental cost-effectiveness of 2-(fluorine-18) fluorodeoxyglucose positron emission tomography (FDG-PET) versus computed tomography (CT) as diagnostic procedures in the primary staging of malignant lymphomas. The study was based on 22 patients of a clinical study who underwent the diagnostic procedures at Ulm University Hospital between April 1997 and May 1998. Direct costs of FDG-PET and CT, including staff, materials, investment, maintenance and overheads, were valued using a micro-costing approach. The effectiveness of both diagnostic procedures was measured as the percentage of correctly staged patients, given a gold standard for staging. The incremental cost-effectiveness ratio was the main outcome measure. Costs per patient of FDG-PET were 257 euros for FDG production and 704 euros for the FGD-PET scan, thus totalling 961 euros (in 1999 prices). The cost per patient of CT scans was found to be 391 euros. Verified PET findings induced an upstaging in four patients such that the effectiveness was 81.8% (18/22) for CT and 100% (22/22) for PET. Incremental cost-effectiveness ratios (interpreted as the additional costs of a more effective diagnostic strategy per additional unit of effectiveness, i.e. additionally correctly staged patient, achieved) were 478 euros per correctly staged patient for CT versus "no diagnostics" and 3133 euros for FDG-PET versus CT. Great potential for cost saving was identified in sensitivity analyses for FDG-PET. It is concluded that diagnostic accuracy and the costs of the diagnostic procedures could be measured precisely. FDG-PET was more accurate than CT. Decision-makers who consider savings in treatment costs significant may find the cost-effectiveness ratio of PET to lie within an acceptable range. However, more research is needed to assess the long-term treatment and cost effects of more accurate staging. There is significant potential to improve the technical efficiency of PET.     

Imaging proliferation in lung tumors with PET: 18F-FLT versus 18F-FDG.

Recently, the thymidine analog 3'-deoxy-3'-(18)F-fluorothymidine (FLT) was suggested for imaging tumoral proliferation. In this prospective study, we examined whether (18)F-FLT better determines proliferative activity in newly diagnosed lung nodules than does (18)F-FDG. METHODS: Twenty-six patients with pulmonary nodules on chest CT were examined with PET and the tracers (18)F-FDG and (18)F-FLT. Tumoral uptake was determined by calculation of standardized uptake value (SUV). Within 2 wk, patients underwent resective surgery or had core biopsy. Proliferative activity was estimated by counting nuclei stained with the Ki-67-specific monoclonal antibody MIB-1 per total number of nuclei in representative tissue specimens. The correlation between the percentage of proliferating cells and the SUVs for (18)F-FLT and (18)F-FDG was determined using linear regression analysis. RESULTS: Eighteen patients had malignant tumors (13 with non-small cell lung cancer [NSCLC], 1 with small cell lung cancer, and 4 with pulmonary metastases from extrapulmonary tumors); 8 had benign lesions. In all visible lesions, mean (18)F-FDG uptake was 4.1 (median, 4.4; SD, 3.0; range, 1.0-10.6), and mean (18)F-FLT uptake was 1.8 (median, 1.2; SD, 2.0; range, 0.8-6.4). Statistical analysis revealed a significantly higher uptake of (18)F-FDG than of (18)F-FLT (Mann-Whitney U test, P < 0.05). (18)F-FLT SUV correlated better with proliferation index (P < 0.0001; r = 0.92) than did (18)F-FDG SUV (P < 0.001; r = 0.59). With the exception of 1 carcinoma in situ, all malignant tumors showed increased (18)F-FDG PET uptake. (18)F-FLT PET was false-negative in the carcinoma in situ, in another NSCLC with a low proliferation index, and in a patient with lung metastases from colorectal cancer. Increased (18)F-FLT uptake was related exclusively to malignant tumors. By contrast, (18)F-FDG PET was false-positive in 4 of 8 patients with benign lesions. CONCLUSION: (18)F-FLT uptake correlates better with proliferation of lung tumors than does uptake of (18)F-FDG and might be more useful as a selective biomarker for tumor proliferation.     

The immunomodulatory properties of in vitro immunoglobulins are dose-dependent

OBJECTIVES: The mechanism by which intravenous immunoglobulins (immunoglobulin G, IgG) exert their beneficial effect on multiple sclerosis (MS) is unknown. Furthermore, there is uncertainty about the optimal dosage of IgG. Therefore, we investigated the influence of different IgG dosages on cytokine production in MS. MATERIALS AND METHODS: Twenty-five MS patients and 15 healthy controls were enrolled. We measured the production of interferon gamma (IFN-gamma), tumour necrosis factor alpha (TNF) and interleukin 10 (IL-10) in peripheral blood lymphocytes by flowcytometry after stimulation without and with IgG in different doses (1, 5 and 10 mg/ml). RESULTS: IFN-gamma and TNF were decreased significantly (P = 0.001) in the untreated and interferon beta (IFN-beta) treated patients after stimulation with IgG. In contrast, IL-10 production was significantly enhanced (P = 0.001) at least in the untreated patient group. The reduction of the pro-inflammatory cytokines IFN-gamma and TNF after stimulation with different IgG doses was clearly dose-dependent in all groups. CONCLUSION: Besides a suppression of the pro-inflammatory cytokines IFN-gamma and TNF, IgG enhances the anti-inflammatory cytokine IL-10. This effect is dose-dependent, speaking in favour of higher IgG doses in the treatment of MS.