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101.
G. C. Korenke H.-J. Christen B. Kruse D. H. Hunneman F. Hanefeld 《Journal of inherited metabolic disease》1997,20(1):59-66
The cerebral phenotype of X-linked adrenoleukodystrophy (ALD) is a rapidly progressive neurodegenerative disorder characterized by a cerebral inflammatory response and elevated very long-chain fatty acids (VLCFA). Interferon- (INFB) is known to suppress the synthesis of tumour necrosis factor and interferon-, which have been reported to be elevated in the margin of the areas of demyelination in ALD brains. We report on treatment with interferon- in 8 patients with cerebral ALD, who additionally received glycerol trioleate/glycerol trierucate. INFB-1a (Rebif, Serono, Switzerland) was given subcutaneously once a week, 3 million units for the first 3 months and 6 million units for the next 9 months. All patients showed an unimpeded progression of neurological symptoms during INFB therapy. Therapy was stopped within 6 months in 4 patients because of the fast neurological deterioration with loss of walking. In all patients the MRI demonstrated a progression of demyelination with a qualitatively unchanged gadolinium enhancement. Further studies are needed to elucidate the pathomechanism of demyelination in ALD in order to find an effective therapy for cerebral ALD patients. 相似文献
102.
Metabolic syndrome represents a cluster of closely connected metabolic diseases as well as hypertension that develops from the common ground of genetic disposition, unhealthy lifestyle and pathogenic psychosocial conditions. The WHO, AHE/NHBLI, IDF and a Saxon Diabetes Expert Committee have published definitions, and the latter a guideline, that define the five components of metabolic syndrome as abdominal obesity, elevated blood pressure, elevated blood glucose levels, elevated triglycerides and low HDL cholesterol values, sometimes presenting varying threshold values. The definitions and guidelines provide a basis for coherent, integrated diagnostics and holistic, rational therapy. 相似文献
103.
Relation of free and specifically bound leptin to insulin secretion in patients with impaired glucose tolerance (IGT). 总被引:1,自引:0,他引:1
W Leonhardt R Horn G Brabant M Breidert T Temelkova-Kurktschiev K Fücker M Hanefeld 《Experimental and clinical endocrinology & diabetes》1999,107(1):46-52
Impaired glucose tolerance (IGT) is frequently associated with an increased fat mass and an altered fat distribution. The adipocyte derived hormone, leptin has been shown to interact with insulin at various levels and may be intimately involved in this process. However, only limited data concerning the interaction of insulin, glucose tolerance and leptin are available and no data exist on the potential influence of bound vs. free circulating leptin. We therefore studied free and bound leptin in 136 patients (77 males, 59 females) with IGT, in relation to plasma glucose, insulin, proinsulin and C-peptide levels as well as serum free and bound leptin concentrations during an oral glucose tolerance test (oGTT). The expected positive relation of free serum leptin levels with body mass index (BMI) was found. Free leptin concentrations were higher in women than in men. Analysis in tertiles revealed a significant relation between free leptin (16-58, 60-160, and 169-932 pmol/l) and mean fasting insulin levels (65, 93, and 100 pmol/l). This relationship remained significant in a multiple regression analysis with BMI and gender as covariates. Similar independent relationships to leptin serum levels were observed for HbA1c and plasma C peptide levels and the proinsulin/insulin ratio but not for plasma glucose and proinsulin levels. These data suggest a fine tuning of leptin by small changes in circulating insulin levels observed in impaired glucose tolerance. 相似文献
104.
Dr Jean-Claude Ansquer Ivan Bekaert Martine Guy Markolf Hanefeld Alain Simon 《Am J Cardiovasc Drugs》2009,9(2):91-101
Background
Patients with type IIb, or mixed, dyslipidemia have high levels of low-density lipoprotein cholesterol (LDL-C) with predominance of small dense LDL particles, high levels of triglycerides (TG), and low levels of high-density lipoprotein cholesterol (HDL-C). Fenofibrate significantly reduces TG and, more moderately, LDL-C, increases HDL-C and produces a shift from small to large LDL particle size; the main effect of ezetimibe is a reduction in LDL-C levels. Combined treatment with fenofibrate and ezetimibe may correct all the abnormalities of type IIb dyslipidemia.Objective
To assess the efficacy and safety of coadministration of fenofibrate (NanoCrystal®) and ezetimibe in patients with type IIb dyslipidemia and the metabolic syndrome compared with administration of fenofibrate and ezetimibe alone (ClinicalTrials.gov Identifier: NCT00349284; Study ID: CLF178P 04 01).Methods
This was a prospective, randomized, double-blind, three-parallel arm, multicenter, comparative study. Sixty ambulatory patients (mean age 56 years; 50% women, 50% men) were treated in each group. For inclusion in the study, patients were required to have LDL-C ≥4.13 mmol/L (≥ 160 mg/dL), TG ≥1.71 mmol/L and ≤4.57 mmol/L (≥150 mg/dL and ≤405 mg/dL), and at least two of the following National Cholesterol Education Program Adult Treatment Panel III criteria for the metabolic syndrome: low HDL-C or increased fasting plasma glucose, blood pressure, or waist circumference. Patients received fenofibrate 145 mg, ezetimibe 10 mg, or coadministration of both (fenofibrate/ezetimibe) daily for 12 weeks. The outcome measures were changes in lipids and related parameters, apolipoproteins, glucose metabolism parameters, and high-sensitivity C-reactive protein (hsCRP).Results
Fenofibrate/ezetimibe was more effective than either fenofibrate or ezetimibe in reducing LDL-C (?36.2% vs ?22.4% and ?22.8%, respectively), non-HDL-C (?36.2% vs ?24.8% and ?20.9%, respectively), total cholesterol (TC) [?27.9% vs ?18.9% and ?17.1%, respectively], apolipoprotein B (?33.3% vs ?24.5% and ?18.7%, respectively), TC/HDL-C ratio (?34.2% vs ?23.0% and ?17.0%, respectively), and apolipoprotein B/apolipoprotein AI ratio (?37.5% vs ?27.0% and ?17.7%, respectively) [p<0.001 for all comparisons between fenofibrate/ezetimibe and monotherapies]. Fenofibrate/ezetimibe was as effective as fenofibrate and more effective than ezetimibe in reducing remnant-like particle cholesterol (?36.2% and ?30.7% vs ?17.3%, respectively), and in increasing LDL size ( + 2.1% and + 1.9% vs + 0.7%, respectively), apolipoprotein AI (+7.9% and + 5.1% vs +0.2%, respectively) and apolipoprotein AII ( + 24.2% and +21.2% vs + 2.7%, respectively). Fenofibrate/ezetimibe and fenofibrate were equally effective in reducing TG (both ?38.3%) and in increasing HDL-C (+11.5% and + 7.9%, respectively; p = 0.282). Ezetimibe had minor effects on TG (?10.4%) and HDL-C ( + 2.2%). Among patients with low HDL-C at baseline (<1.29 mmol/L [<50 mg/dL] in women, <1.03 mmol/L [<40 mg/dL] in men), normalization of HDL-C was observed in 52.9% with fenofibrate/ezetimibe and in 58.8% with fenofibrate, compared with 20.0% with ezetimibe. Changes in hsCRP were ?25.9% with fenofibrate/ezetimibe, ?27.8% with fenofibrate, and ?10.2% with ezetimibe (not statistically significant). None of the treatments altered glucose metabolism parameters.Conclusion
In patients with type IIb dyslipidemia and features of the metabolic syndrome, coadministration of fenofibrate 145 mg and ezetimibe 10 mg daily was more effective than either monotherapy in reducing LDL-C, non-HDL-C, apolipoprotein B, and cardiovascular risk ratios, and was as effective as fenofibrate 145 mg alone in reducing TG and in increasing HDL-C in patients with low baseline HDL-C levels. 相似文献105.
Thirteen patients who had undergone prolonged adrenocorticotropic hormone (ACTH) therapy for infantile spasms or myoclonic encephalopathy were examined with sonography. Nine patients were found to have appearances characteristic of medullary nephrocalcinosis. In each of these infants the cortical echogenicity was normal in the presence of focal areas of increased echogenicity within the renal pyramids. Five patients also showed a homogeneously increased echogenicity of the whole pancreas on sonography, and two of these showed increased density on computed tomography. Density measurements were in the range of calcific material within the papillae and pancreatic tissue. On abdominal survey radiographs, even in retrospect no calcifications could be recognized. 相似文献
106.
107.
Pfützner A Hanefeld M Dekordi LA Müller J Kleine I Fuchs W Forst T 《Journal of diabetes science and technology》2011,5(4):989-998
Aims
This study investigated the effects of pioglitazone (PIO), ramipril (RAM), or their combination (PIRA) on low-grade inflammation in nondiabetic hypertensive patients with increased cardiovascular risk.Methods and Results
Patients enrolled in this placebo-controlled, double-blind, randomized, parallel trial (72 male, 77 female, aged 60 ± 9 years, body mass index 30.4 ± 4.7 kg/m2, duration of hypertension 9 ± 8 years) were treated with either 30/45 mg PIO (dose titration), 2.5/5 mg RAM, or their combination for 12 weeks. A reduction in high-sensitivity C-reactive protein was observed with PIO (−0.89 ± 1.98 mg/liter; -25%) and PIRA (−0.49 ± 2.11 mg/liter; -16%), while an increase was seen with RAM (0.58 ± 2.13 mg/liter; +20%, p < .05 vs PIO and PIRA). The 24-hour blood pressure profile showed a small increase with both monotherapies but a decrease with PIRA (p < .05 vs PIO). Improvements in biomarkers of chronic systemic inflammation and insulin resistance (IR) were observed in the PIO and PIRA arms only [PIO/RAM/PIRA: homeostasis model of assessment of IR: -0.78 ± 1.39 (−29%)/0.15 ± 1.03 (+5%)/ -1.44 ± 2.83 (−40%); adiponectin: 8.51 ± 5.91 (+104%)/ 0.09 ± 2.63 (+1%)/ 8.86 ± 6.37 mg/liter (+107%); matrix metallo-proteinase-9: -48 ± 127 (−12%)/-1 ± 224 (0%)/-60 ± 210 ng/ml (−13%), p < .05 for RAM vs PIO or PIRA in all cases].Conclusions
Our 3-month study in nondiabetic hypertensive patients showed a decrease in biomarkers of IR and chronic systemic inflammation with the PIO monotherapy and the PIRA combination only, which may help to explain some findings in other cardiovascular outcome trials. 相似文献108.
Comparison of the serological responses to Moraxella catarrhalis immunoglobulin D-binding outer membrane protein and the ubiquitous surface proteins A1 and A2 下载免费PDF全文
Tan TT Christensen JJ Dziegiel MH Forsgren A Riesbeck K 《Infection and immunity》2006,74(11):6377-6386
Moraxella catarrhalis immunoglobulin D-binding protein (MID) is a complex antigen with unique immunoglobulin D (IgD)-binding, adhesion, and hemagglutination properties. Previous studies have shown that antibodies raised against MID764-913 in rabbits inhibited M. catarrhalis adhesion to human alveolar epithelial cells, and immunization with MID764-913 resulted in an increased pulmonary clearance in a murine model. Strong immune responses against MID have also consistently been shown in humans. Here, the MID-specified IgG responses were compared to those of ubiquitous surface proteins A1 and A2 (UspA1/A2) using a series of recombinant fragments that spanned all three proteins. Sera were obtained from young children, aged 6 months to 1 year (n = 8) and 2 to 3 years (n = 15), and healthy adults (n = 16). Acute- and convalescent-phase sera from chronic obstructive pulmonary disease (COPD) patients with M. catarrhalis infective exacerbations (n = 23) were also analyzed. Young children, who are at risk of M. catarrhalis infection, had low levels of anti-MID and anti-UspA1/A2 antibodies. Healthy adults and the majority of COPD patients (16/23) had high levels of antibodies directed against, among others, the adhesive domain of MID and the fibronectin- and C3-binding domains of UspA1/A2. Among eight COPD patients in whom a rise in antibody levels could be detected, these functional domains were also the main regions targeted by the antibodies. In addition, human IgG directed against MID was bactericidal and anti-MID antibodies were additive to antibodies targeting UspA1/A2. Hence, the functional domains in these three antigens may have significant potential in a future vaccine against M. catarrhalis. 相似文献
109.
Markolf KL Feeley BT Jackson SR McAllister DR 《The American journal of sports medicine》2006,34(4):604-611
BACKGROUND: Objective results of posterior cruciate ligament reconstruction are often less than satisfactory, with many patients exhibiting excessive posterior laxity. HYPOTHESIS: Changes in the position of the femoral tunnel within the posterior cruciate ligament's femoral footprint will significantly affect anteroposterior laxities and graft forces. STUDY DESIGN: Controlled laboratory study. METHODS: The posterior cruciate ligament's femoral origin was mechanically isolated in 13 fresh-frozen knee specimens, and the bone cap containing the ligament's insertion was attached to a load cell that recorded resultant force during tibial loading tests. Anteroposterior laxity (at +/- 200 N applied force) was also measured. Cast acrylic replicas of the bone cap were fabricated, with tunnels placed in anterolateral, central, and posteromedial regions of the footprint. A graft reconstruction was tested in each tunnel. RESULTS: Mean laxities with the anterolateral tunnel were +0.9 mm to +1.7 mm greater than normal between 0 degrees and 45 degrees of flexion. Mean laxities with the posteromedial tunnel were -2.4 mm to -3.7 mm less than normal between 10 degrees and 45 degrees of flexion. Mean laxities with the central tunnel were not significantly different from intact knee values, except at 0 degrees (0.9 mm greater). Mean graft forces with the anterolateral tunnel were normal for most modes of loading, whereas there were significant increases in graft forces with the posteromedial and central tunnels. CONCLUSION: The anterolateral tunnel reproduced normal posterior cruciate ligament force profiles but produced a knee that was more lax than normal between 0 degrees and 45 degrees of flexion. The central tunnel best matched intact knee laxities, but graft forces were higher than posterior cruciate ligament forces between 0 degrees and 45 degrees of flexion. The posteromedial tunnel overconstrained anteroposterior laxity approximately 2 to 4 mm between 0 degrees and 45 degrees of flexion and generated higher graft forces in the same flexion range. CLINICAL RELEVANCE: This study suggests that a posteromedial tunnel should not be used for single-bundle posterior cruciate ligament reconstruction. 相似文献
110.
Per Henrik Borgstrom Keith L. Markolf Brock Foster Frank A. Petrigliano David R. McAllister 《Knee surgery, sports traumatology, arthroscopy》2014,22(9):2064-2069