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Arterial dysfunction has been documented in patients with beta-thalassaemia major. This study aimed to determine the quantity
and proliferative capacity of circulating CD133+VEGFR2+ and CD34+VEGFR2+ cells in patients with beta-thalassaemia major and those after haematopoietic stem cell transplantation (HSCT), and their
relationships with arterial function. Brachial arterial flow-mediated dilation (FMD), carotid arterial stiffness, the quantity
of these circulating cells and their number of colony-forming units (CFUs) were determined in 17 transfusion-dependent thalassaemia
patients, 14 patients after HSCT and 11 controls. Compared with controls, both patient groups had significantly lower FMD
and greater arterial stiffness. Despite having increased CD133+VEGFR2+ and CD34+VEGFR2+ cells, transfusion-dependent patients had significantly reduced CFUs compared with controls (p = 0.002). There was a trend of increasing CFUs across the three groups with decreasing iron load (p = 0.011). The CFUs correlated with brachial FMD (p = 0.029) and arterial stiffness (p = 0.02), but not with serum ferritin level. Multiple linear regression showed that CFU was a significant determinant of FMD
(p = 0.043) and arterial stiffness (p = 0.02) after adjustment of age, sex, body mass index, blood pressure and serum ferritin level. In conclusion, arterial dysfunction
found in patients with beta-thalassaemia major before and after HSCT may be related to impaired proliferation of CD133+VEGFR2+ and CD34+VEGFR2+ cells. 相似文献
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Purpose
The antiretroviral therapy era has shifted the epidemiology of HIV-associated diseases, increasing the recognition of non-infectious pulmonary complications secondary to HIV. We aimed to determine the association between CD4+, viral load, and pulmonary function in individuals with uncontrolled HIV, and determine how changes in these parameters are associated with pulmonary function longitudinally.Methods
This is a retrospective observational study of individuals with HIV who underwent pulmonary function testing in an urban medical center between August 1997 and November 2015.Results
Of the 146 participants (mean age 52 ± 10 years), 49% were Hispanic, 56% were men, and 44% were current smokers. CD4+ <200 cells/μl was associated with significant diffusion impairment compared to CD4+ ≥200 cells/μl (DLCO 56 vs. 70%, p = <0.01). VL (viral load) ≥75 copies/ml was associated with significant diffusion impairment compared to VL <75 copies/ml (DLCO 60 vs. 71%, p = <0.01). No difference in FEV1, FEV1/FVC, or TLC was noted between groups. In univariate analysis, CD4+ and VL correlated with DLCO (r = +0.33; p = <0.01; r = ?0.26; p = <0.01) and no correlation was noted with FEV1, FEV1/FVC, or TLC. Current smoking and history of AIDS correlated with DLCO (r = ?0.20; p = 0.03; r = ?0.20; p = 0.04). After adjusting for smoking and other confounders, VL ≥75 copies/ml correlated with a 11.2 (CI 95% [3.03–19.4], p = <0.01) decrease in DLCO. In Spearman’s Rank correlation, there was a negative correlation between change in VL and change in DLCO over time (ρ = ?0.47; p = <0.01).Conclusion
The presence of viremia in individuals with HIV is independently associated with impaired DLCO. Suppression of VL may allow for recovery in diffusing capacity over time, though the degree to which this occurs requires further investigation.5.
Stephen Zano Yasanandana S. Wijayasinghe Radhika Malik Joshua Smith Ronald E. Viola 《Journal of inherited metabolic disease》2013,36(1):1-6
Canavan disease (CD) is a fatal neurological disorder caused by defects in the gene that encodes for a critical metabolic enzyme. The enzyme aspartoacylase catalyzes the deacetylation of N-acetylaspartate to produce acetate required for fatty acid biosynthesis in the brain. The loss of aspartoacylase activity leads to the demyelination and disrupted brain development that is found in CD patients. Sixteen different clinical mutants of aspartoacylase have been cloned, expressed and purified to examine their properties and the relationship between enzyme properties and disease phenotype. In contrast to numerous cell culture studies that reported virtually complete loss of function, each of these purified mutant enzymes was found to have measureable catalytic activity. However, the activities of these mutants are diminished, by as little as three-fold to greater than 100-fold when compared to the native enzyme. Many of these mutated enzyme forms show decreased thermal stability and an increased propensity for denaturation upon exposure to urea, but only four of the 16 mutants examined showed both diminished thermal and diminished conformational stability. Significantly, each of these lower stability mutants are responsible for the more severe phenotypes of CD, while patients with milder forms of CD have aspartoacylase mutants with generally high catalytic activity and with either good thermal or good conformational stability. These results suggest that the loss of catalytic function and the accumulation of N-acetylaspartate in Canavan disease is at least partially a consequence of the decreased protein stability caused by these mutations. 相似文献
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Giannini EG Malfatti F Botta F Polegato S Testa E Fumagalli A Mamone M Savarino V Testa R 《Digestive diseases and sciences》2005,50(7):1207-1213
Helicobacter pylori eradication therapy is commonly prescribed in the general population. Treatment consists of drugs that are mainly metabolized by the liver cytochrome P-450 (CYP) enzymatic pool. Most H. pylori-infected patients often take drugs for comorbid illnesses, therefore increasing the potential for drug–drug interactions. We aimed to evaluate the interactions of rabeprazole, clarithromycin, and metronidazole 1-week H. pylori eradication therapy with CYP-dependent liver metabolic function in clinical practice. Ten patients referred to our unit for H. pylori infection underwent 1-week eradication therapy with rabeprazole (20 mg, b.i.d.), clarithromycin (500 mg, b.i.d.), and metronidazole (500 mg, b.i.d.). We chose the 13C-aminopyrine breath test (13C-ABT) to evaluate CYP-dependent liver function since it is noninvasive and nonharmful. All patients underwent 13C-ABT at three time points: before therapy (t0), at the end of therapy (t8), and after 1 month of follow-up (t38). Mean 13C-ABT dose/hr (t0 = 14.0 ± 5.4, t8 = 13.5 ± 4.0, t38 = 16.1 ± 5.6) as well as 13C-ABT cumulative dose (t0 = 2.4 ± 1.1, t8 = 2.4 ± 0.8, t38 = 2.6 ± 1.0) were not statistically different at the three time points of the study. These results did not seem to be influenced by drugs being administered concomitantly. In everyday clinical practice rabeprazole-based H. pylori eradication therapy does not seem to display any significant interactions with CYP-dependent liver function, even in patients on multiple drugs.Disclosure: None of the authors received funding to carry out this study or has a financial interest in companies producing the drugs used in the study. 相似文献
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Carageorgiou H Pantos C Zarros A Stolakis V Mourouzis I Cokkinos D Tsakiris S 《Metabolic brain disease》2007,22(1):31-38
Thyroid hormones (THs) are recognized as key metabolic hormones, and the metabolic rate increases in hyperthyroidism, while
it decreases in hypothyroidism. The aim of this work was to investigate how changes in metabolism induced by THs could affect
the activities of acetylcholinesterase (AChE), (Na+, K+)- and Mg2+-ATPase in the hypothalamus and the cerebellum of adult rats. Hyperthyroidism was induced by subcutaneous administration of
thyroxine (25μg/100 g body weight) once daily for 14 days, while hypothyroidism was induced by oral administration of propylthiouracil
(0.05%) for 21 days. All enzyme activities were evaluated spectrophotometrically in the homogenated brain regions of 10 three-animal
pools. Neither hyper-, nor hypothyroidism had any effect on the examined hypothalamic enzyme activities. In the cerebellum,
hyperthyroidism provoked a significant decrease in both the AChE (−23%, p < 0.001) and the Na+, K+-ATPase activities (−26%, p < 0.001). Moreover, hypothyroidism had a similar effect on the examined enzyme activities: AChE (−17%, p < 0.001) and Na+, K+-ATPase (−27%, p < 0.001). Mg2+-ATPase activity was found unaltered in both the hyper- and the hypothyroid brain regions. In conclusion: neither hyper-,
nor hypothyroidism had any effect on the examined hypothalamic enzyme activities. In the cerebellum, hyperthyroidism provoked
a significant decrease in both the AChE and the Na+, K+-ATPase activities. The decreased (by the THs) Na+, K+-ATPase activities may increase the synaptic acetylcholine release, and thus, could result in a decrease in the cerebellar
AChE activity. Moreover, the above TH-induced changes may affect the monoamine neurotransmitter systems. 相似文献
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Xuefang Ren Kozaburo Akiyoshi Arthur A. Vandenbark Patricia D. Hurn Halina Offner 《Metabolic brain disease》2011,26(1):87-90
Experimental cerebral ischemic stroke is exacerbated by inflammatory T-cells and is accompanied by systemic increases in CD4+CD25+Foxp3+ regulatory T-cells (Treg). To determine their effect on ischemic brain injury, Treg were depleted in Foxp3DTR mice prior to stroke induction. In contrast to a recent Nature Medicine report, our results demonstrate unequivocally that
Treg depletion did not affect stroke infarct volume, thus failing to implicate this regulatory pathway in limiting stroke
damage. 相似文献
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Aims/hypothesis
Several genome-wide linkage studies have shown an association between diabetic nephropathy and a locus on chromosome 18q harbouring two carnosinase genes, CNDP1 and CNDP2. Carnosinase degrades carnosine (β-alanyl-l-histidine), which has been ascribed a renal protective effect as a scavenger of reactive oxygen species. We investigated the putative associations of genetic variants in CNDP1 and CNDP2 with diabetic nephropathy (defined either as micro- or macroalbuminuria) and estimated GFR in type 2 diabetic patients from Sweden. 相似文献11.
Susanne Keiding Michael Sørensen Ole Lajord Munk Dirk Bender 《Metabolic brain disease》2010,25(1):49-56
Dynamic 13N-ammonia PET is used to assess ammonia metabolism in brain, liver and muscle based on kinetic modeling of metabolic pathways,
using arterial blood 13N-ammonia as input function. Rosenspire et al. (1990) introduced a solid phase extraction procedure for fractionation of 13N-content in blood into 13N-ammonia, 13N-urea, 13N-glutamine and 13N-glutamate. Due to a radioactive half-life for 13N of 10 min, the procedure is not suitable for blood samples taken beyond 5–7 min after tracer injection. By modifying Rosenspire’s
method, we established a method enabling analysis of up to 10 blood samples in the course of 30 min. The modified procedure
was validated by HPLC and by 30-min reproducibility studies in humans examined by duplicate 13N-ammonia injections with a 60-min interval. Blood data from a 13N-ammonia brain PET study (from Keiding et al. 2006) showed: (1) time courses of 13N-ammonia fractions could be described adequately by double exponential functions; (2) metabolic conversion of 13N-ammonia to 13N-metabolites were in the order: healthy subjects > cirrhotic patients without HE > cirrhotic patients with HE; (3) kinetics
of initial tracer distribution in tissue can be assessed by using total 13N-concentration in blood as input function, whereas assessment of metabolic processes requires 13N-ammonia measurements. 相似文献
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Gao Z Biersack HJ Ezziddin S Logvinski T An R 《Journal of cancer research and clinical oncology》2004,130(11):649-656
Purpose The medical treatment of metastatic medullary thyroid carcinoma (MTC) is still questionable. The aim of this study was to evaluate a combined imaging protocol using 111In-DTPA-octreotide and 131I/123I-MIBG to decide whether targeted radiotherapy would be useful, and which radiopharmaceutical (90Y-DOTATOC or 131I-MIBG) would be more effective.Methods Eight patients (four men, four women; mean age 61 years) with metastatic MTC were included. Treatments were performed with 3,330 MBq 90Y-DOTATOC at 6-week intervals, or 11.1 GBq 131I-MIBG with a minimum interval of 3 months.Results The imaging procedure was positive in all eight patients: 111In-DTPA-octreotide imaging in five patients, 131I/123I-MIBG imaging in four patients. With respect to the number of metastatic lesions, MIBG imaging was less effective than octreotide. According to the results of combined imaging, we identified one patient to be treated with 90Y-DOTATOC, and three patients with 131I-MIBG. An overall antitumor effect was observed in all four patients, one with partial remission and three with stable disease. No relevant toxicity was observed.Conclusions The combined imaging can increase the detection rate of metastatic foci in patients with MTC and identify more patients for effective radionuclide treatment. The treatment with 90Y-DOTATOC or 131I-MIBG is well tolerated and may improve the fate of patients with metastatic MTC. 相似文献
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PURPOSE Conventional practice in colorectal surgery involves stoma education being imparted postoperatively. Proficiency in stoma management often delays patients discharge following colorectal surgery. The aim of this randomized, controlled trial was to compare preoperative intensive, community-based stoma education with conventional postoperative stoma education after elective colorectal surgery.METHODS Forty-two elective colorectal patients requiring a stoma were randomized into an intensive preoperative teaching (study) or postoperative (control) group. Intervention for the study group included two preoperative visits in the community during which patients were taught with audiovisual aids to use and change the stoma pouching system. Goal-directed postoperative stoma education was standardized for both groups. Outcomes measured included time to stoma proficiency, postoperative hospital stay, unplanned stoma-related interventions in the community within six weeks of discharge, and preoperative and postoperative hospital anxiety and depression scores. Cost-effectiveness of the intervention was also evaluated.RESULTS All outcomes measured were improved in the study group, including time to stoma proficiency(5.5 vs. 9 days; P = 0.0005), hospital stay (8 vs. 10 days; P
= 0.029), and unplanned stoma-related community interventions per patient (median 0 vs. 0.5; P = 0.0309). No adverse effects of the intervention were noted. The average cost saving per patient was £1,119 ($2,104) for the study group compared with the control group.CONCLUSIONS Stoma education is more effective if undertaken in the preoperative setting. It results in shorter times to stoma proficiency and earlier discharge from the hospital. It also reduces stoma-related interventions in the community and has no adverse effects on patient well-being.Supported in part by Coloplast Limited, Peterborough, United Kingdom.Read at the annual meeting of The American Society of Colon and Rectal Surgeons, Dallas, Texas, May 8 to 13, 2004. 相似文献
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Bjørnvold M Undlien DE Joner G Dahl-Jørgensen K Njølstad PR Akselsen HE Gervin K Rønningen KS Stene LC 《Diabetologia》2008,51(4):589-596
Background/hypothesis HLA, INS, PTPN22 and CTLA4 are considered to be confirmed type 1 diabetes susceptibility genes. HLA, PTPN22 and CTLA4 are known to be involved in immune regulation. Few studies have systematically investigated the joint effect of multiple
genetic variants. We evaluated joint effects of the four established genes on the risk of childhood-onset type 1 diabetes.
Methods We genotyped 421 nuclear families, 1,331 patients and 1,625 controls for polymorphisms of HLA-DRB1, −DQA1 and −DQB1, the insulin gene (INS, −23 HphI), CTLA4 (JO27_1) and PTPN22 (Arg620Trp).
Results The joint effect of HLA and PTPN22 on type 1 diabetes risk was significantly less than multiplicative in the case-control data, but a multiplicative model could
not be rejected in the trio data. All other two-way gene–gene interactions fitted multiplicative models. The high-risk HLA
genotype conferred a very high risk of type 1 diabetes (OR 20.6, using the neutral-risk HLA genotype as reference). When including
also intermediate-risk HLA genotypes together with risk genotypes at the three non-HLA loci, the joint odds ratio was 61 (using
non-risk genotypes at all loci as reference).
Conclusion Most established susceptibility genes seem to act approximately multiplicatively with other loci on the risk of disease except
for the joint effect of HLA and PTPN22. The joint effect of multiple susceptibility loci conferred a very high risk of type 1 diabetes, but applies to a very small
proportion of the general population. Using multiple susceptibility genotypes compared with HLA genotype alone seemed to influence
the prediction of disease only marginally.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users. 相似文献
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