Quantitative T2 mapping of the patella at 3.0T is sensitive to early cartilage degeneration, but also to loading of the knee.

OBJECTIVE: The aim of the study was to explore the sensitivity and robustness of T2 mapping in the detection and quantification of early degenerative cartilage changes at the patella. MATERIALS AND METHODS: Forty-two patients (22 women, 20 men) with a mean age of 30.3 years and a symptomatic cartilage defect of ICRS grade ≤2 were examined using a 3T MRI with an 8-channel knee coil. The cartilage lesion was graded based on high-resolution PD TSE and 3D isotropic TrueFISP images. T2 maps were calculated from a standard MESE-sequence, performed at the beginning and at the end of the scan (40min in-between). Depending on the defect size, a region-of-interest (ROI) analysis was performed on 1-3 consecutive slices. Mean T2 values for the deep, superficial, and global layer as well as the zonal variation were compared among defect grades (ANOVA, post hoc Duncan-test) and over time (Student's t-test). RESULTS: T2-measurements directly correlated with the extent of cartilage defect (ICRS grade) at all layers and at both time-points. However, correlations were closer for the second measurement at the end of the scan. In this unloaded state, differences in T2-values became more pronounced and were significant even between cartilage of normal appearance adjacent to the defect and healthy cartilage of control patients (both ICRS grade 0). In contrast, there were no such differences among grades in the zonal variation at any time. CONCLUSION: T2 mapping might be a sensitive method for the detection of early cartilage degeneration at the patella in the unloaded joint.

A prospective observational study of anaemia management in cancer patients - results from the German Cancer Anaemia Registry.

The use of erythropoiesis-stimulating agents (ESA) in cancer patients is still under debate. However, little is known about rationales, strategies, objectives, and effectiveness of anaemia treatments in common practice. The Cancer Anaemia Registry prospectively surveyed about 2000 cancer patients with anaemia throughout Germany. The main objectives of anaemia treatment regardless of modality were to improve quality of life (QOL) and to correct haemoglobin (Hb) levels. The Hb threshold for any anaemia treatment (means ± SD: 9.4 ± 1.2 g/dL) but not for blood transfusions (8.7 ± 1.0 g/dL) depended on cancer type and treatment strategy. Physicians preferred ESA as first-line treatment to prevent transfusions in patients with solid tumours, if they thought that chemotherapy caused the anaemia. If they suspected other causes or patients had lymphoproliferative malignancies, physicians preferred transfusions or attempted to correct underlying disorders; both mainly to improve QOL or prognosis. Effectiveness of all strategies was comparable. However, ESA most effectively prevented transfusions; primary transfusions appeared less suitable for correcting Hb or improving QOL. Using supportive treatments for QOL improvement was common whereas diagnostic measures and intravenous iron therapy were underused. Prospective clinical trials using QOL as end point and evaluating diagnostics in cancer-associated anaemia are warranted.

Echinacea purpurea along with zinc, selenium and vitamin C to alleviate exacerbations of chronic obstructive pulmonary disease: results from a randomized controlled trial.

WHAT IS KNOWN AND OBJECTIVE: Upper respiratory tract infections (URTI) frequently cause exacerbations of chronic-obstructive pulmonary disease (COPD). Stimulation of the innate immune system may provide an early defence against such infections. The objective of this study was to determine whether Echinacea purpurea (EP) along with micronutrients may alleviate COPD exacerbations caused by acute URTI. METHODS: This was a double-blind, randomized, placebo-controlled trial in COPD patients with acute URTI. Patients were given ciprofloxacin for 7 days and additionally one tablet per day of EP, of EP along with zinc, selenium and ascorbic acid (EP+), or of placebo until day 14. Serum levels of TNF α and interleukins 1ß, 6 and 10 were measured before and after treatment. Until week 4 post-end of treatment, all patients had to daily report on COPD symptoms in diaries. RESULTS AND DISCUSSION: In total, 108 mostly male patients with a mean age of 65·8 years (40-81 years) were enrolled. Patients of the three treatment arms did not vary significantly in baseline characteristics. EP+, but not EP resulted in significantly less severe and shorter exacerbation episodes following URTI as compared with placebo suggesting a synergistic effect of Echinacea and micronutrients. Large variations in biomarkers in-between and within groups were unrelated to treatment. Study medication was safe and well tolerated with overall 15 adverse events one of which was serious. Among those, sleeping disorders were most frequent and likely related to the underlying disease. WHAT IS NEW AND CONCLUSION: The combination of EP, zinc, selenium and vitamin C may alleviate exacerbation symptoms caused by URTI in COPD. Further studies are warranted to investigate the interactions among Echinacea, zinc, selenium and vitamin C.

Hemoglobin levels that trigger erythropoiesis-stimulating agent treatment decisions for cancer-associated anemia--examination of practice in Germany.

OBJECTIVE: Given the safety concerns regarding off-label use of erythropoiesis-stimulating agents (ESAs) in the treatment of cancer-associated anemia, data from the German Cancer Anemia Registry (CAR) were analyzed to examine whether current practice in Germany adheres to treatment guidelines. RESEARCH DESIGN AND METHODS: CAR was a web-based registry gathering patient data for 12 weeks following anemia diagnosis or until the primary treatment objective was achieved. RESULTS: Of over 2000 patients surveyed, 783 were treated with ESAs. Treatment was primarily aimed at improvement of quality of life (37.3%), hemoglobin correction (32.7%), and prevention of transfusions (24.4%). The average hemoglobin level triggering ESA treatment was 9.7 g/dL (6.0 mmol/L), however, starting levels varied with cancer type. For 67.8% of patients, transfusions could be avoided. ESA treatment was stopped at 11.2 g/dL (7.0 mmol/L) and maximum hemoglobin levels during the study averaged 11.8 g/dL (7.3 mmol/L). In 4.8% of the women and 6.0% of the men, maximum hemoglobin levels were >14 g/dL (8.7 mmol/L); in 15.6% and 9.1%, respectively, levels were between 13 and 14 g/dL. The median hemoglobin level triggering transfusion was 8.3 g/dL (5.2 mmol/L), irrespective of the malignant disease. CONCLUSION: Current use of ESAs for the treatment of cancer-associated anemia in Germany appears to be in good compliance with treatment guidelines. Similar results obtained from other studies in Europe and the US indicate this to be true beyond Germany.

Preferential usage of TCR-Vbeta17 by peripheral and cutaneous T cells in nickel-induced contact dermatitis.

Nickel (Ni) is one of the most common contact sensitizers in man, and Ni-induced contact dermatitis is considered as a model of hapten-induced delayed type hypersensitivity. Previous studies indicated that Ni-reactive T cells derived from Ni-allergic individuals preferentially express distinct TCR-Vbeta chains. However, data on the TCR-Vbeta repertoire of Ni-responsive T cells are not consistent. Therefore, the aim of this study was to identify the TCR-Vbeta receptors of Ni-responsive peripheral and cutaneous T cells in a cohort of 17 donors with Ni-induced contact dermatitis in comparison with those of 6 healthy controls. Peripheral NiSO(4)-responsive T lymphocytes showed a significant overexpression of TCR-Vbeta17 and the frequency of TCR-Vbeta17(+) T cells correlated significantly with the in vitro reactivity of PBMC to NiSO(4). In addition, the cutaneous infiltrate of Ni-induced patch test reactions consisted primarily of Vbeta17(+) T cells. The majority of patch test-derived NiSO(4)-responsive T cells of three allergic donors were TCR-Vbeta17(+), whereas patch test-derived NiSO(4) unresponsive T cells of four additional donors did not express TCR-Vbeta17. Skin-derived Ni-responsive T cell lines from three donors uniformly secreted the Th2 cytokine, IL-5, but no IFN-gamma or IL-10. These in vitro and in vivo findings strongly suggest that T cells with a restricted TCR-Vbeta repertoire, i.e., Vbeta17, predominate in NiSO(4)-induced contact dermatitis and may be crucial in the effector phase of Ni hypersensitivity.

The autumnal fattening of the long-distance migratory garden warbler (Sylvia borin) is stimulated by intermittent fasting.

To investigate the proximate influence of a changing food availability on the seasonal fattening of migratory birds, garden warblers (Sylvia borin) following postnuptial moult were food restricted once a week. Body mass, food intake, plasma hormone and metabolite levels were measured and compared to birds which always had ad libitum food access. The food-restricted birds increased their body mass significantly earlier than the controls. The accelerated fattening was initially not accompanied by hyperphagia and may be due to either an increased food utilisation efficiency or a reduced metabolic rate. An increase of basal glucagon and corticosterone and a decrease of insulin levels prior to fattening were not significant, however, they resulted in a significant decrease of the insulin:glucagon ratio. This ratio was also lower in food-restricted birds than in control birds and may account for the difference in the fattening progress. We conclude that seasonal fattening may be stimulated by a catabolic impulse which could be imposed in free-living birds by a decrease of food availability and/or by an increase of energy expenditure. A negative energy balance is hypothesised to be a common proximate factor affecting migratory as well as winter fattening.

The influence of fasting on blood and plasma composition of herring gulls (Larus argentatus).

Populations of scavenging seabird species in the North Sea may fluctuate with an artificial food source: the availability of fishery waste. To document this impact, it is necessary to assess the birds' nutritional status during periods with decreased fishing activity. Reference data for this purpose was collected from 22 herring gulls investigated during laboratory fasting. After 6 d of food deprivation and body mass losses exceeding 15%, the first birds entered starvation phase 3. Comparatively, this is a rather weak fasting capacity. Plasma levels of total protein and thyroid hormones decreased and beta-hydroxybutyrate increased with fasting duration. The leucocyte proportions were shifted from lymphocytes to heterophils. After 3 d of refeeding, most of the fasting changes were reversed. Plasma enzyme activities increased and hematocrit, hemoglobin, and erythrocyte numbers decreased in both fasting and control birds, most likely as a result of experimental stress and repeated blood sampling. Glucose, cholesterol, monocytes, basophils, and glycosylated hemoglobin remained fairly constant. Triglycerides, free fatty acids, uric acid, and urea varied significantly, but changes were not as clearly a result of fasting. Therefore, total protein, beta-hydroxybutyrate, triiodothyronine, thyroxine, and lymphocyte and heterophil percentages may be the most reliable indicators of the nutritional status and the condition of free-living herring gulls.

Fasting increases the plasma glucagon response in the migratory garden warbler (Sylvia borin).

Acute pancreatic hormonal responses to oral glucose loads were investigated in garden warblers during the prolonged fast that follows their autumnal migratory fattening. Plasma glucose, free fatty acids, beta-hydroxybutyrate, insulin (INS), and glucagon (GLN) were measured prior to and 10 min after an oral glucose load in three groups of birds: One had food ad libitum, and the other two were either food restricted or food deprived down to a given (low) body mass level. Ten minutes after the glucose load, plasma glucose levels increased significantly in all three groups (range of mean values: basal, 15.1-16.0; glucose-stimulated, 19.1-23.7 mmol/L). A smaller increase in food-restricted/deprived groups was not statistically significant. Free fatty acid levels (1.0-1.5 mmol/L) after 10 min were unchanged, while beta-hydroxybutyrate decreased to similar levels in food-restricted/deprived and control groups (basal, 3.3-4.2; glucose-stimulated, 1.9-2.4 mmol/L). Insulin increased and glucagon decreased in response to oral glucose loads. However, initial levels and responses of plasma insulin to glucose were lower, and those of glucagon were higher in the food-restricted/deprived groups (INS, both 2.7; DeltaINS, 0.1-0.3 mIU/L; GLN, 2.8-3.3; DeltaGLN, 1.4-2.2 microg/L) than in the control group (means +/- SE; INS, 3.8 +/- 0.8; DeltaINS, 1.4 +/- 0.7 mIU/L; GLN, 2.5 +/- 0.5; DeltaGLN, 0.7 +/- 0.5 microg/L), resulting in similar increases in the insulin:glucagon ratio. Impaired insulin secretion may thus be compensated for by a greater glucagon response and the decreased glucose utilization rates of fasting garden warblers may result from insulin resistance and/or delayed glucose absorption.

Glucose utilization rate and pancreatic hormone response to oral glucose loads are influenced by the migratory condition and fasting in the garden warbler (Sylvia borin).

Substrate utilization and regulatory mechanisms of metabolism were studied in migratory garden warblers by measuring plasma levels of glucose, free fatty acids (FFAs), beta-hydroxybutyrate, insulin and glucagon in response to oral glucose loads. Three different physiological states were examined: (a) the autumnal migratory period on a high and (b) on a fasted low body mass level, and (c) the postmigratory period with low body mass. Glucose tolerance was better in the postmigratory lean than fat condition. However, total food deprivation of 5-7 days with fat birds reaching their lean body mass further reduced the glucose utilization rate. Initial levels of FFAs were highest in the starved, intermediate in the fat and lowest in the lean condition. Changes in plasma FFAs during glucose tolerance tests were opposite to those of the glucose levels. Ten minutes after the glucose load plasma glucagon levels decreased and insulin increased. These effects were larger in the fat than in the postmigratory lean condition. There were no differences between sexes. It appears that during premigratory and migratory periods glucose utilization may be inhibited by a more favorable oxidation of fatty acids as would be predicted by the glucose fatty acid cycle. However, the inhibition of glucose utilization seems to be counterregulated by stronger responses of insulin and glucagon. These results may be important also in the consideration of food selection during premigratory periods and refueling abilities of birds crossing ecological barriers.

A role for pancreatic hormones in the regulation of autumnal fat deposition of the garden warbler (Sylvia borin)?

Glucagon and insulin were measured by heterologous immunoassays in plasma samples of 17 garden warblers (Sylvia borin) kept under constant ad libitum or fasting-refeeding conditions during the migratory season from September to May. Plasma levels of key metabolic indicators (glucose, triglycerides, cholesterol, and free fatty acids) were measured every 2 weeks. Measurements of the two hormones concur with the general assumption of a higher glucagon:insulin ratio, indicating a more pronounced catabolism in birds than in mammals. The concentrations of both hormones varied (insulin: 0.7-7.7 microIU/ml, n = 66; glucagon: 0.4-4.5 ng/ml, n = 99), but differences between mean values per month were significant only for glucagon. Neither hormone titer correlated with either the seasonal or a fasting-refeeding-induced body mass cycle. However, there was a positive correlation between food intake, changes in body mass, and plasma triglycerides and insulin; in contrast, there was a negative relationship with the glucagon:insulin ratio. Glucagon showed only a small negative relationship to plasma glucose and cholesterol, but correlated directly more closely with plasma free fatty acids. The present data support the fact that glucagon is more lypolytic in birds than in mammals. Pancreatic hormones are suggested to participate in the regulation of premigratory hyperphagia and hyperlipemia.