Citations

Purpose High-grade gliomas (HGGs; WHO grades 3-4) are highly diverse, with survival times ranging from months to years. WHO 2000 grading criteria for high-grade oligodendroglial neoplasms [anaplastic oligoastrocytoma (AOA) and anaplastic oligodendroglioma (AO)] remain subjective, and the existence of grade 4 variants is controversial. Patients and Methods Overall survival (OS) of 1,093 adult patients with a cerebral HGG newly diagnosed between 1990 and 2005 was analyzed by univariate and multivariate models for significance of the following factors: patient age, surgery type, year of diagnosis, endothelial proliferation, necrosis, oligodendroglial histology, treatment center, and chromosome 1p, 19q, 7p (EGFR), and 10q (PTEN) abnormalities by fluorescence in situ hybridization (FISH). Results Necrosis was a statistically significant predictor of poor OS on univariate and multivariate analyses in AOA but not in AO. Median OS for patients with necrotic AOA (22.8 months) was significantly worse than for patients with non-necrotic AOA (86.9 months; P < .0001) but was better than conventional glioblastomas (9.8 months; P < .0001). In addition to patient age, the following were significant independent prognostic factors (P ≤ .001): grade and surgery type for the entire HGG cohort; modified grade for AOA (3 v 4); and modified grade, 1p/19q codeletion status, and oligodendroglial histology for the 586 HGGs analyzed by FISH. Conclusion Stratification of AOA, but not of pure AO, into grades 3 and 4 on the basis of necrosis is prognostically justified and is more powerful than the current approach. Both routine histology and genetic testing provide independent, prognostically useful information.

Objective: Although the epidemiology of microscopic colitis has been described in Europe, no such data exist from North America. We studied the incidence, prevalence and temporal trends of microscopic colitis in a geographically defined US population. Design and setting: In this population based cohort study, residents of Olmsted County, Minnesota, with a new diagnosis of microscopic colitis, and all who had colon biopsies for evaluation of diarrhoea, between 1 January 1985 and 31 December 2001 were identified. Biopsies were reviewed for confirmation (cases) and to identify missed cases (diarrhoea biopsies). Main outcome measures: Incidence rates, age and sex adjusted to the 2000 US white population. Poisson regression assessed the association of calendar period, age and sex with incidence. Results: We identified 130 incident cases for an overall rate of 8.6 cases per 100 000 person-years. There was a significant secular trend, with incidence increasing from 1.1 per 100 000 early in the study to 19.6 per 100 000 by the end (p<0.001). Rates increased with age (p<0.001). By subtype, the incidence was 3.1 per 100 000 for collagenous colitis and 5.5 per 100 000 for lymphocytic colitis. Collagenous colitis was associated with female sex (p<0.001) but lymphocytic colitis was not. Prevalence (per 100 000 persons) on 31 December 2001 was 103.0 (39.3 for collagenous colitis and 63.7 for lymphocytic colitis). Conclusions: The incidence of microscopic colitis has increased significantly over time, and by the end of the study, the incidence and prevalence were significantly higher than reported previously. Microscopic colitis is associated with older age, and collagenous colitis is associated with female sex.

AbstractPrevious studies with macrophages that had been prelabeled with [14C]arachidonic acid (20∶4) have shown that condensed tannin is a potent agonist for the release of arachidonic acid. However, it has not been demonstrated that the percentage release of [14C]20∶4 accurately reflects the metabolic activity of the endogenous 20∶4 pool. In order to measure the 20∶4 mass release relative to the total cellular 20∶4 pool, the free fatty acids of freshly isolated alveolar macrophages were derivatized with a fluorescent reagent, and then separated and quantified by high‐performance liquid chromatography. The amounts of esterified fatty acids were measured by gas chromatography of the methyl esters. Free fatty acid levels were compared to those of the total esterified plus unesterified fatty acids to determine the actual percentage released of each fatty acid. Tannin‐stimulated release of 20∶4 mass reflected that previously reported for the release of [14C]20∶4 label but at a slower rate and at a much lower percentage indicating that [14C]20∶4 had been incorporated into part of a more reactive pool. The specificity of the fatty acid release induced by tannin and β‐1,3‐glucan, a known agonist for 20∶4 release, was also examined. Both agonists promoted an increase in the levels of free 20∶4 and of other fatty acids. A comparison of the absolute increases of each of the fatty acids indicated that tannin caused a preferential increase in the mass of free 20∶4, whereas β‐1,3‐glucan evoked a selective increase in the mass of 16∶0.

AbstractThirty‐nine urbanized ethnic Namibian people comprising 21 Bushmen (semi‐urbanized), 7 Hereros and 11 Kavangos were assessed for plasma lipids and fatty acid (FA) composition. Total cholesterol and triacylglycerol concentrations were measured by enzymatic methods, and neutral lipid FA composition by gas‐liquid chromatography. The results demonstrated that while total cholesterol concentrations were not significantly different, significant differences in triacylglycerol concentrations (P<0.05) were seen between Bushmen and Kavangos. By comparing Bushmen with Hereros and Kavangos, significant differences between Bushmen and Kavangos were also observed in plasma triacylglycerol FA compositions, particularly 16∶0 (32.73%vs. 25.05%), 16∶1n−7 (7.00%vs. 5.06%), 18∶2n−6 (9.30%vs. 22.25%) and 20∶3n−6 (0.12%vs. 0.48%), while Kavangos had higher 20∶4n−6 levels than Hereros (1.44%vs. 2.00%). In plasma cholesteryl esters, Bushmen were significantly different from Kavangos in 16∶1n−7 (8.85%vs. 4.93%), 18∶1n−9 (32.06%vs. 23.07%) and 20∶4n−6 (6.91%vs. 10.00%). Significant differences were also observed between Bushmen and Hereros in 18∶0 (1.08%vs. 1.29%) and 18∶2n−6 (35.68%vs. 45.50%). The FA of Namibian groups were also compared with South African reference groups comprising urbanized whites and Xhosas and rural Vendas. The differences in blood lipid values can be explained primarily by excessive alcohol consumption. These results suggest that semi‐urbanized Bushmen have changed their diets under urbanized conditions which may increase their risk of coronary heart disease.

AbstractLipid and apolipoprotein (apo) A‐I concentrations in different density fractions of New Zealand White (NZW) and Watanabe (WHHL) rabbit plasma were studied. Aside from the low plasma apoA‐I and high density lipoprotein (HDL) cholesterol levels in WHHL rabbits, the distribution of apoA‐I was also different between the two rabbits. ApoA‐I was concentrated in both the HDL2 and HDL3 fractions of NZW rabbits but was found primarily in the HDL3 fraction of WHHL rabbits. ApoA‐I secretion in these two rabbits was further studiedin vitro by using intestinal and hepatocyte cell cultures. ApoA‐I secretion was highest from cultures of the duodenum and the proximal end of the jejunum; whereas, cell cultures of the distal end of the small intestine secreted very little apoA‐I into the medium. Intestinal cell cultures from WHHL rabbits secreted less, but significant amounts of, apoA‐I compared to that of NZW rabbits. ApoA‐I was most concentrated in the density range of 1.12–1.21 (HDL3) fraction in medium containing 10% fetal calf serum (FCS). Serum‐free medium promoted apoA‐I secretion by intestinal cell cultures that was mostly found in the d>1.21 (lipoprotein‐deficient) fraction. Hepatocytes isolated from the same rabbits by collagenase perfusion secreted little apoA‐I, and it was found only in the d>1.21 fraction. The addition of oleic acid into the culture medium with 10% FCS decreased the secretion of total apoA‐I and HDL by intestinal cell cultures and increased the secretion of very low density lipoprotein (VLDL) and intermediate density lipoproteins (IDL). The results indicate that intestinal cells, not hepatocytes, are responsible for the secretion of apoA‐I and HDL3 in rabbits, and that the secretion may be regulated under different nutritional conditions.

AbstractThree of six kin were identified, by high performance thin layer chromatography, capillary gas chromatography and mass spectrometry, as having phytanic acid storage disease. Phytanic acid was found in triacylglycerol and, to a lesser degree, in phosphatidylcholine and free fatty acids. An unsaturated analogue of phytanic acid was additionally identified in plasma and erythrocyte triacylglycerols. In plasma, branched chain fatty acids were primarily localized in the low density lipoprotein fraction. The concentration of plasma major fatty acids was not affected by the presence of these branched chain fatty acids. In contrast to plasma, only small amounts of phytanic acid were found in cerebrospinal fluid and biopsied sural nerve. The nerve phytanate was mainly associated with triacylglycerol in epineurial and perineurial tissues. Lack of phytanate accumulation in sural endoneurium, even in cases with severe fiber degeneration, suggests that demyelination in Refsum's disease may not be due to myelin instability resulting from the incorporation of branched chain fatty acids into peripheral nerve membrane.

Thirty-two subjects with impaired fasting glucose (IFG) and 28 subjects with normal fasting glucose (NFG) ingested a labeled meal and 75 g glucose (oral glucose tolerance test) on separate occasions. Fasting glucose, insulin, and C-peptide were higher (P &lt; 0.05) in subjects with IFG than in those with NFG, whereas endogenous glucose production (EGP) did not differ, indicating hepatic insulin resistance. EGP was promptly suppressed, and meal glucose appearance comparably increased following meal ingestion in both groups. In contrast, glucose disappearance (Rd) immediately after meal ingestion was lower (P &lt; 0.001) in subjects with IFG/impaired glucose tolerance (IGT) and IFG/diabetes but did not differ in subjects with IFG/normal glucose tolerance (NGT) or NFG/NGT. Net insulin action (Si) and insulin-stimulated glucose disposal (Si*) were reduced (P &lt; 0.001, ANOVA) in subjects with NFG/IGT, IFG/IGT, and IFG/diabetes but did not differ in subjects with NFG/NGT or IFG/NGT. Defective insulin secretion also contributed to lower postprandial Rd since disposition indexes were lower (P &lt; 0.001, ANOVA) in subjects with NFG/IGT, IFG/IGT, and IFG/diabetes but did not differ in subjects with NFG/NGT and IFG/NGT. We conclude that postprandial hyperglycemia in individuals with early diabetes is due to lower rates of glucose disappearance rather than increased meal appearance or impaired suppression of EGP, regardless of their fasting glucose. In contrast, insulin secretion, action, and the pattern of postprandial turnover are essentially normal in individuals with isolated IFG.