Exercise capacity and cardiac function in type 1 diabetic patients treated with continuous subcutaneous insulin infusion. A controlled study

In order to investigate the effect of improved glycaemic control on exercise capacity and cardiac function, bicycle exercise and echocardiography at rest and after exercise was performed in 24 short-term type 1 diabetic patients, randomized to conventional insulin therapy (CIT) or to continuous subcutaneous insulin infusion (CSII). After 6 months significant improvement in glycaemic control was seen in the CSII group showing a decrease in mean blood glucose and haemoglobin A1c (HbA1c), while no change was observed in the CIT group. Exercise capacity increased by 24% (p less than 0.01) in the CSII group and decreased by 16% (NS) in the CIT group. In the CSII group fractional shortening of the left ventricle during rest decreased by 14% (p less than 0.02), while an increase of 2% (NS) was seen in the CIT group. Further, changes of left ventricular fractional shortening during rest were inversely correlated to changes in exercise capacity. After exercise, fractional shortening of the left ventricle and rate-pressure product was unchanged in the two groups. In conclusion this study shows a beneficial effect of improved glycaemic control induced by CSII on exercise capacity possibly by reducing resting state demands to the cardiovascular system.     

骨形态发生蛋白4转基因治疗大鼠的胫骨缺损

目的:观察基因工程技术构建人骨形态发生蛋白4复制缺陷腺病毒的成骨效果。方法:实验于2006-03/08在安徽医科大学第一附属医院实验动物中心完成。实验分组:选取普通级雄性SD大鼠30只,体质量(200±10)g,全部动物胫骨上端部分分别造成8mm×5mm长方形缺损。采用自身对照法,右侧骨缺损为实验组,左侧骨缺损为对照组。实验组植入人骨形态发生蛋白4复制缺陷腺病毒复合明胶海绵,对照组植入单纯明胶海绵。实验评估:术后分别于4,6,8周麻醉后处死10只动物,取材行X线、组织病理、免疫组织化学、透视电镜检查,观察成骨情况。结果:纳入30只大鼠,全部进入结果分析。①大鼠胫骨缺损X线、组织病理学检查结果:术后8周实验组和对照组骨缺损均得到修复,但实验组无论从成骨时间、成骨效果、新生骨量等方面都要优于对照组。其中各时间点实验组骨密度明显高于对照组,差异有显著性意义[4周:(95.91±16.33),(87.93±11.52);6周:(128.34±10.64),(102.41±9.81);8周:(138.36±10.49),(121.56±9.63);P<0.01]。各时间点实验组新生骨占骨缺损面积比明显高于对照组,差异有显著性意义[4周:(41.39±5.65)%,(26.58±5.62)%;6周:(80.35±7.25)%,(65.41±6.52)%;8周:(96.45±2.76)%,(82.22±7.30)%;P<0.01]②术后4周免疫组织化学染色结果:实验组软骨及骨痂内呈强阳性反应,而对照组骨痂内骨形态发生蛋白4表达微弱。结论:人骨形态发生蛋白4重组腺病毒具有良好的成骨活性,骨形态发生蛋白4直接转基因治疗能够加快骨缺损的修复。     

Arterial concentration of 99mTc-sestamibi at rest, during peak exercise and after dipyridamole infusion

Tracers for myocardial perfusion imaging during stress should not only have high cardiac uptake but they should also have a fast blood clearance to prevent myocardial tracer uptake after the ischaemic stimulus. The present study characterize the early phase of the arterial (99m)Tc-sestamibi (MIBI) time-activity curve after venous bolus injection at rest, during peak exercise and after dipyridamole infusion. We included 11 patients undergoing angioplasty for one-vessel disease (rest study) and 20 patients evaluated for the detection of haemodynamic significant coronary stenoses by (99m)Tc-sestamibi single photon emission computed tomography (SPECT) using either bicycle exercise testing (10 patients) or standard dipyridamole testing (10 patients). Arterial blood samples of 1 ml were taken from the left femoral artery (rest study) or the right radial artery (exercise and dipyridamole studies) every 5 s during the first 5 min postinjection. In the exercise and the dipyridamole studies blood sampling were extended to include blood samples every 5 min 5-30 min postinjection. Peak MIBI concentration was lower and decrease in concentration slower after tracer injection during exercise than during dipyridamole stress testing. This may cause an underestimation of perfusion defects during exercise because of MIBI uptake after the ischaemic stimulus. The implications of the study not only refer to the choice of stress modality when using MIBI. This study also underlines the importance of considering early blood clearance in addition to regional myocardial tracerkinetic aspects such as myocardial extraction fraction when new tracers are introduced.     

IVUS radiofrequency analysis in the evaluation of the polymeric struts of the bioabsorbable everolimus‐eluting device during the bioabsorption process

Background : In the ABSORB study cohort A the changes in the amount of dense calcium and necrotic core have not been reported in comparison to the prestenting phase; this evaluation could be useful to better clarify the bioabsorption process. Aim of this study was therefore to evaluate the dynamic changes in plaque size and plaque tissue composition observed between 6 months and 2 years follow‐up, and to compare these findings to the prestenting phase. Methods : Angiography, intravascular ultrasound and derived parameters (virtual histology, palpography, and echogenicity) were serially assessed postprocedure, at 6 months and at 2 years in 20 patients. In a subset of 8 patients the same measurements were also recorded in the prestenting phase. Results : In the total population a reduction of 18% in the plaque area was observed between 6 month and 2 year follow‐up (7.56 ± 2.32 mm² at 6 months vs. 6.16 ± 2.10 mm² at 2 year follow‐up; P < 0.01). In the subgroup of eight patients who underwent IVUS during the pre‐stenting phase, the plaque area at 2 year follow‐up was not significantly different when compared to the prestenting plaque area (7.29 ± 2.29 mm² at prestenting vs. 7.48 ± 1.45 mm² at 2 year follow‐up, P = NS). Necrotic core area was reduced by 24% between the 6 month and 2 year follow‐up (0.97 ± 0.66 mm² at 6 months vs. 0.74 ± 0.53 mm² at 2 year follow‐up; P = NS), whilst dense calcium was reduced by 14% from 6 month to 2 year follow‐up (0.83 ± 0.50 mm² at 6 months vs 0.72 ± 0.64 mm² at 2 year follow‐up; P = NS). Whilst the necrotic core at 2 years follow‐up was not significantly different when compared to the pre‐stenting phase (0.62 ± 0.42 mm² prestenting vs 1.07 ± 0.56 mm² at 2 year follow‐up; P = NS), the area of dense calcium was significantly higher at follow‐up compared to prestenting (0.35 ± 0.35 mm² pre‐stenting vs. 0.84 ± 0.66 mm² at 2 year follow‐up; P < 0.05). Conclusions : The reduction in the necrotic core component between 6 month and two year follow‐up could be related to a synergistic effect of the bio‐absorption process and the anti‐inflammatory action of everolimus. © 2010 Wiley‐Liss, Inc.     

Five‐year long‐term clinical follow‐up of the XIENCE V everolimus eluting coronary stent system in the treatment of patients with de novo coronary artery lesions: The SPIRIT FIRST trial

Background : Drug‐eluting stents have shown to be superior over bare metal stents in clinical and angiographic outcomes after percutaneous treatment of coronary artery stenosis. However, long‐term follow‐up data are scarce and only available for sirolimus‐ and paclitaxel‐eluting stents. Aim : To assess the feasibility and performance of the XIENCE V everolimus‐eluting stent (EES) versus an identical bare metal stent after a 5‐year follow‐up period. Methods : SPIRIT FIRST was a First in Man, multicentre, prospective, single‐blind, clinical trial, randomizing 60 patients with a single de novo coronary artery lesion in a ratio of 1:1 to either an everolimus eluting or a bare metal control stent. Results : At 5‐year clinical follow‐up, data were available in 89% and 86% of patients in the everolimus and control arm, respectively. In the everolimus arm, no additional death, myocardial infarction, clinically driven target lesion revascularization (TLR), or clinically driven target vessel revascularization (TVR) events were observed between 1‐ and 5‐year follow‐up. The 5‐year hierarchical major adverse cardiac events (MACE) and target vessel failure (TVF) rates for the everolimus arm were 16.7% (4/24) for both endpoints. In the control group, no additional cardiac death, myocardial infarction, or clinically driven TLR events were observed between 2‐ and 5‐year follow‐up. No additional clinically driven TVR events were observed between 3‐ and 5‐year follow‐up. The 5‐year hierarchical MACE and TVF rates for the control arm were 28.0% (7/25) and 36.0% (9/25), respectively. No stent thromboses were observed in either the everolimus arm or the control arm up to 5 years. Conclusion : The favorable 5‐year long term clinical outcome of the EES is consistent with the results from other studies of the EES with shorter follow‐up. © 2010 Wiley‐Liss, Inc.     

Influence of clinical status on the association between plasma total and unbound bilirubin and death or adverse neurodevelopmental outcomes in extremely low birth weight infants

Objectives: To assess the influence of clinical status on the association between total plasma bilirubin and unbound bilirubin on death or adverse neurodevelopmental outcomes at 18–22 months corrected age in extremely low birth weight infants. Method: Total plasma bilirubin and unbound bilirubin were measured in 1101 extremely low birth weight infants at 5 ± 1 days of age. Clinical criteria were used to classify infants as clinically stable or unstable. Survivors were examined at 18–22 months corrected age by certified examiners. Outcome variables were death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death prior to follow‐up. For all outcomes, the interaction between bilirubin variables and clinical status was assessed in logistic regression analyses adjusted for multiple risk factors. Results: Regardless of clinical status, an increasing level of unbound bilirubin was associated with higher rates of death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss and death before follow‐up. Total plasma bilirubin values were directly associated with death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death before follow‐up in unstable infants, but not in stable infants. An inverse association between total plasma bilirubin and death or cerebral palsy was found in stable infants. Conclusions: In extremely low birth weight infants, clinical status at 5 days of age affects the association between total plasma bilirubin and death or adverse neurodevelopmental outcomes at 18–22 months of corrected age. An increasing level of UB is associated a higher risk of death or adverse neurodevelopmental outcomes regardless of clinical status. Increasing levels of total plasma bilirubin are directly associated with increasing risk of death or adverse neurodevelopmental outcomes in unstable, but not in stable infants.     

Detection of fetal red cells in fetomaternal hemorrhage using a fetal hemoglobin monoclonal antibody by flow cytometry

BACKGROUND: The laboratory determination of the level of fetal cells in maternal circulation remains an important support in the obstetrical management of women with suspected uterine trauma and in the proper dose administration of anti-D for prevention of Rh hemolytic disease of the newborn. Limitations in the sensitivity and precision of the widely used manual Kleihauer-Betke test have prompted an increased utilization of flow cytometric methods for fetal cell detection in maternal blood samples. STUDY DESIGN AND METHODS: Murine monoclonal antibodies directed against fetal hemoglobin (HbF) were developed, conjugated to fluorescein isothiocyanate, and used in a multiparametric flow cytometric assay developed for the quantitation of fetal red cells. A rapid intracellular staining method using brief glutaraldehyde fixation and Triton X-100 permeabilization prior to monoclonal antibody incubation was developed, along with optimization of the flow cytometric analysis protocol for the analysis of 50,000 cells. The performance of the assay was assessed for linearity and precision and correlated with the Kleihauer-Betke acid elution method. RESULTS: The anti-HbF flow cytometric method showed good correlation with the Kleihauer-Betke method (r2 = 0.86) and superior precision with a CV < 15 percent for blood samples with > 0.1 percent fetal cells. Analysis of 150 blood samples from nonpregnant adults, including individuals with elevated HbF due to hemoglobinopathies and hereditary persistence of HbF, gave a mean value of 0.02 percent fetal cells, and all results were less than 0.1 percent. CONCLUSIONS: The anti-HbF flow cytometric method for detection of fetal cells offers a simple, reliable, and more precise alternative to the Kleihauer-Betke manual technique for the assessment of fetomaternal hemorrhage. The method has additional potential applications for the study of HbF levels or frequency of adult red cells with low levels of HbF (F cells) in individuals with hemoglobinopathies.     

Purification of Hageman factor (factor XII) on columns of popcorn- agarose

Purification of Hageman factor (HF, factor XII) from human plasma is a tedious procedure and the product is not always in the precursor form. Hojima has described a protein derived from corn kernels that inhibits the enzymatic properties of HF. This inhibitor binds to the precursor form of HF. Rapid purification of HF was achieved by using as the major purification step adsorption of this clotting factor to popcorn inhibitor bound to agarose. The product had a specific activity of 50.0 to 67.1 coagulant units of HF per milligram protein, and the yield was 33% to 40% of the HF content of the starting plasma. The purified protein displayed a single band upon unreduced or reduced sodium dodecyl sulfate polyacrylamide gel electrophoresis and less than 0.1% was in an activated form, as measured in coagulant assays. The technique described is more rapid and reliable than methods described earlier.