Incidental colonic focal lesions detected by FDG PET/CT

OBJECTIVE: The aim of this study was to assess the performance of FDG PET/CT for the detection of colonic lesions, especially advanced neoplasms (villous or >10-mm adenomas, carcinomas). Because of 18F FDG accumulation in adenomatous polyps, PET using FDG can detect early premalignant colorectal lesions. MATERIALS AND METHODS: FDG PET/CT studies performed for a 1-year period in 1,716 consecutive patients with various malignant diseases, except colorectal cancer, were retrospectively reviewed. PET images obtained 1 hr after FDG injection and non-contrast CT images used for attenuation correction were fused for analysis. Of 45 patients showing intense focal colonic FDG uptake, 20 patients (with 21 foci) underwent a colonoscopic investigation, and, when necessary, polyp resection. The intensity of FDG uptake was quantified using the standardized uptake value (SUV(max)). RESULTS: The FDG colonic foci were associated with 18 colonoscopic abnormalities in 15 patients, with no colonic abnormality detected in five patients (false-positive [FP] results). Histopathologic findings revealed advanced neoplasms in 13 patients (13 villous adenomas and three carcinomas) and two cases of hyperplastic polyps. A difference in the mean SUV(max) was found between FP and true-positive colonic FDG foci but was not statistically significant (p = 0.14). CONCLUSION: Presence of a focal colonic FDG uptake incidental finding on a PET/CT scan justifies a colonoscopy to detect (pre-)malignant lesions. The fusion of PET and CT images allows an accurate localization of the lesions. PET/CT is a useful tool to differentiate pathologic from physiologic FDG uptake.     

Vascular smooth muscle cell endovascular therapy stabilizes already developed aneurysms in a model of aortic injury elicited by inflammation and proteolysis

OBJECTIVE: To investigate the efficiency of endovascular smooth muscle cell (VSMC) seeding in promoting healing and stability in already-developed aneurysms obtained by matrix metalloproteases (MMPs)-driven injury. SUMMARY BACKGROUND DATA: VSMCs are instrumental in arterial healing after injury and are in decreased number in arterial aneurysms. This cellular deficiency may account for poor healing capabilities and ongoing expansion of aneurysms. METHODS: Aneurysmal aortic xenografts in rats displaying extracellular matrix injury by inflammation and proteolysis were seeded endoluminally with syngeneic VSMCs, with controls receiving culture medium only. Diameter, structure, and the destruction/reconstruction balance were assessed. RESULTS: Eight weeks after endovascular infusion, aneurysmal diameter had increased further, from 3.0 +/- 0.3 mm to 10.9 +/- 6.5 mm (P = 0.009), and medial elastin content had decreased from 36.5 +/- 8.5 to 5.2 +/- 5.5 surface-percent (S%; P = 0.009) in controls, whereas these parameters remained stable in the seeded group (3.0 +/- 0.3 to 2.7 +/- 0.2 mm, P = 0.08; 36.5 +/- 8.4 to 31.6 +/- 9.7 S%, P = 0.22). VSMC seeding was followed by a decrease in mononuclear infiltration. MMP-1, -3, -7, -9, and -12 mRNA contents were sharply decreased in the diseased wall in response to seeding. Tissue inhibitor of metalloproteinase-1, -2, and -3 mRNAs in the intima were increased in a 2 to 10 magnitude in comparison with controls. Gelatin zymography showed the disappearance of MMP-9 activity and reverse zymography a strong increase in tissue inhibitor of metalloproteinase-3 activity in the seeded group. VSMC-seeded aneurysms were rich in collagen and lined with an endothelium instead of a thrombus in controls. CONCLUSIONS: VSMCs endovascular seeding restores the healing capabilities of proteolytically injured extracellular matrix in aneurysmal aortas, and stops expansion.     

The sources of hospital cost variability

Hospital heterogeneity is a major issue in defining a reimbursement system. If hospitals are heterogeneous, it is difficult to distinguish which part of the differences in costs is due to cost containment efforts and which part cannot be reduced, because it is due to other unobserved sources of hospital heterogeneity. In this paper, we apply an econometric approach to analyse hospital cost variability. We use a nested three-dimensional database (stays-hospitals-years) in order to explore the sources of variation in hospital costs, taking into account unobservable components of hospital cost heterogeneity. The three-dimensional structure of our data makes it possible to identify transitory and permanent components of hospital cost heterogeneity. Econometric estimates are performed on a sample of 7314 stays for acute myocardial infarction (AMI) observed in 36 French public hospitals over the period 1994-1997. Transitory unobservable hospital heterogeneity is far from negligible: its estimated standard error is about 50% of the standard error we estimate for cost variability due to permanent unobservable heterogeneity between hospitals.     

Plantar soft-tissue thickness predicts high peak plantar pressure in the diabetic foot

The aim of this study was to evaluate whether high plantar foot pressures can be predicted from measurements of plantar soft-tissue thickness in the forefoot of diabetic patients with neuropathy. A total of 157 diabetic patients with neuropathy and at least one palpable foot pulse but without a history of foot ulceration were invited to participate in the study. Plantar tissue thickness was measured bilaterally at each metatarsal head, with patients standing on the same standardized platform. Plantar pressures were measured during barefoot walking using the optical pedobarograph. Receiver operating characteristic analysis was used to determine the plantar tissue thickness predictive of elevated peak plantar pressure. Tissue thickness cutoff values of 11.05, 7.85, 6.65, 6.55, and 5.05 mm for metatarsal heads 1 through 5, respectively, predict plantar pressure at each respective site greater than 700 kPa, with sensitivity between 73% and 97% and specificity between 52% and 84%. When tissue thickness was used to predict pressure greater than 1,000 kPa, similar results were observed, indicating that high pressure at different levels could be predicted from similar tissue thickness cutoff values. The results of the study indicate that high plantar pressure can be predicted from plantar tissue thickness with high sensitivity and specificity.     

The dietary glycemic index during pregnancy: influence on infant birth weight, fetal growth, and biomarkers of carbohydrate metabolism

During pregnancy, lower levels of maternal glucose before and during a glucose load have been associated with reduced infant birth weight and an increased risk of small-for-gestational-age births. A lower incremental area under the glucose response curve defines a low glycemic diet. Thus, during pregnancy the maternal diet, as measured by the glycemic index, may influence fetal growth and infant birth weight. A total of 1,082 gravidas who enrolled in the Camden Study between August 1996 and October 2002 were followed prospectively during pregnancy. The dietary glycemic index was computed from three 24-hour recalls in the course of pregnancy. Samples for plasma glucose and for glycosylated hemoglobin were obtained at 24-28 weeks' gestation. The glycemic index was positively and significantly related to maternal glycosylated hemoglobin and plasma glucose. There were as well significant linear trends for dietary fat intake to decrease and for intakes of carbohydrate, sucrose, fiber, and folate to increase as the glycemic index declined. Gravidas with a low dietary glycemic index had reduced infant birth weight and approximately a twofold increased risk of a small-for-gestational-age birth. Consistent with data on maternal plasma glucose, data in this study show that the type of carbohydrate in the diet of urban, low-income women influences fetal growth and infant birth weight.     

Triplex-forming oligonucleotides - sequence-specific DNA ligands as tools for gene inhibition and for modulation of DNA-associated functions

The down regulation of gene expression is a promising strategy for molecular medicine and experimental biology. Molecules that bind to the DNA double helix may interfere with gene expression and, in addition to potential therapeutic applications, can be helpful for the investigation of DNA processing, chromatin package, or associated biological processes. Triplex-forming oligonucleotides (TFOs) bind to specific sequences in the DNA double helix via hydrogen bonding interactions. TFOs have been shown to down-regulate gene expression, to induce targeted genomic DNA modifications, to stimulate DNA recombination, and to modulate chromatin organization. Additionally, they may be used as carriers to position DNA-modifying agents to selected sequences. TFO-mediated effects have been mostly described in cell culture, but one study reported TFO activity in a mouse model. Critical issues regarding TFO-based technologies are the development of new oligonucleotide analogues with improved binding affinity, better target selectivity, and sufficient stability in the intracellular environment. A prerequisite for the development of such DNA-binding molecules is the availability of appropriate methods to assess their binding properties quantitatively at the desired target sequence in the genome. This review focuses on recent results regarding gene-inhibitory effects of TFOs in cell culture and methods to evaluate TFO-binding to the desired target sequence in the context of the human genome.     

Antiangiogenic properties of fibstatin, an extracellular FGF-2-binding polypeptide

By using the two-hybrid system with basic fibroblast growth factor (FGF-2) as bait, we isolated and characterized fibstatin, an endogenous M(r) 29,000 human basement membrane-derived inhibitor of angiogenesis and tumor growth. Fibstatin, a fragment containing the type III domains 12-14 of fibronectin, was produced as a recombinant protein and was shown to inhibit the proliferation, migration, and differentiation of endothelial cells in vitro. Antiangiogenic activity of fibstatin was confirmed in a Matrigel angiogenesis assay in vivo, and electrotransfer of the fibstatin gene into muscle tissue resulted in reduced B16F10 tumor growth. Taken together, these results suggest that fibstatin could act as a powerful molecule for antiangiogenic therapy.     

Obesity and colon cancer: Does leptin provide a link?

Obesity, a risk factor for colorectal cancer, is associated with elevated serum levels of leptin, the adipocyte-derived hormone, and insulin. Experimental and epidemiologic studies have indicated a role for insulin in the pathogenesis of colon cancer, and recent experimental studies have suggested a similar role for leptin. In a case-control study nested in the Janus Biobank, Norway, we measured serum levels of leptin and C-peptide (a marker of pancreatic insulin secretion) in cryopreserved prediagnostic sera from men (median age, 45 years) who were diagnosed with cancer of the colon (n = 235) or rectum (n = 143) after blood collection (median time, 17 years), and among 378 controls matched for age and date of blood collection. Conditional logistic regression analyses showed an approximately 3-fold increase in colon cancer risk with increasing concentrations of leptin up to an odds ratio (OR) of 2.72 (95% CI = 1.44-5.12) for top vs. bottom quartile (p(trend) = 0.008). The corresponding OR for C-peptide was 1.81 (95% CI = 0.67-4.86; p(trend) = 0.19). The risk estimates remained unchanged after mutual adjustment. No association of hormone levels with rectal cancer risk was found. Reproducibility of hormone measurements assessed by intraclass coefficients (ICCs) for paired samples taken 1 year apart was high for leptin (ICC = 0.82) but lower for C-peptide (ICC = 0.30). Our results suggest that leptin is a risk factor for colon cancer, and that leptin may provide a link between obesity and colon cancer. Leptin may be directly involved in colon tumorigenesis or it may serve as a sensitive and robust marker of an obesity-induced adverse endocrine environment. Only weak support for an association of insulin with colon cancer was found.