EFFICACY OF RAMIPRIL VERSUS ENALAPRIL IN PATIENTS WITH MILD TO MODERATE ESSENTIAL HYPERTENSION

SUMMARY This double-blind, randomised, cross-over study investigated the antihypertensive efficacy of ramipril and enalapril was completed by 30 patients with mild-to-moderate essential hypertension. After a four-week placebo run-in phase, the patients received either 2.5mg ramipril or 10mg enalapril once daily for four weeks. The dosages were increased to 5mg ramipril and 20mg enalapril for a further four weeks. After a placebo washout phase of four weeks, the patients were crossed over to the alternative treatment. The decrease in average 24-hour ambulatory diastolic blood pressure from week 0 to week 8 was 1.6mmHg greater with ramipril than enalapril (90% confidence interval 0.6-2.7mmHg). The corresponding reduction in for systolic blood pressure was also greater with ramipril than enalapril by 2.4mmHg (90% confidence interval: 0.5-4.2mmHg). For the difference in the drop of 24-hour ambulatory diastolic blood pressure between ramipril and enalapril the lower level of the 90% confidence interval (CI) is above the clinically relevant difference of -3mmHg. This is an indication that ramipril (2.5 and 5mg dose) is at least as effective as enalapril (10 and 20mg dose) in decreasing blood pressure in patients with mild-to-moderate essential hypertension. The duration of adequate antihypertensive effect was relatively long for both ramipril and enalapril; however, ramipril tended to have a more prolonged antihypertensive effect. Ramipril had a higher diastolic and systolic trough/peak ratio than enalapril, resulting in a more uniform antihypertensive effect over the 24-hour treatment period. Both ramipril and enalapril were well tolerated and the two treatment groups had similar safety profiles.     

Sensitivity of serum concentration of cartilage biomarkers to 21‐days of bed rest

The objective of the study was to test the hypothesis that serum levels of cartilage oligomeric matrix protein (COMP) would decrease and serum levels of tumor‐necrosis factor alpha (TNF‐α) and selected matrix metalloproteinases (MMPs) would increase in response to bed rest (BR) and that these changes are unaffected by the intake of potassium bicarbonate or whey protein. Seven and nine healthy male subjects participated in two 21‐day 6° head down tilt crossover BR‐studies with nutrition interventions. Serum samples were taken before, during, and after BR and biomarker concentrations were measured using commercial enzyme‐linked immunosorbent assays. MMP‐3 during BR was significantly lower than at baseline (reduction greater 20%; p < 0.001). MMP‐3 increased significantly from 14 to 21 days of BR (+7%; p = 0.049). COMP during BR was significantly lower than at baseline (reduction greater 20%; p < 0.001). MMP‐3 and COMP returned to baseline within 1 day after BR. MMP‐9 on day 3 of BR was significantly lower than at baseline (?31%; p < 0.033) and on days 3, 5, and 14 of BR significantly lower than at the end of and after BR (reduction greater 35%; p < 0.030). The nutritional countermeasures did not affect these results. The observed changes in cartilage biomarkers may be caused by altered cartilage metabolism in response to the lack of mechanical stimulus during BR and inflammatory biomarkers may play a role in changes in biomarker levels. Clinical relevance: Immobilization independently from injury can cause altered cartilage biomarker concentration. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1465–1471, 2018.

     

Influence of patellar ligament insertion angle on quadriceps usage during walking in anterior cruciate ligament reconstructed subjects

Reduced quadriceps contraction has been suggested as an adaptation to prevent anterior tibial translation in anterior cruciate ligament (ACL)-deficient knees. This theory has been supported by a recent study that peak knee flexion moment (thought to be created by a decrease of quadriceps contraction) during walking was negatively correlated with patellar ligament insertion angle (PLIA) in ACL-deficient knees, but not in contralateral, uninjured knees. In addition, the PLIA was significantly smaller in ACL-deficient knees than in contralateral, uninjured knees. However, it is unknown whether ACL reconstruction restores the PLIA or whether the relationship between the PLIA and knee flexion moments previously observed in ACL-deficient knees disappears. This study tested the following hypotheses: (1) The PLIA of ACL-reconstructed knees is significantly smaller than the PLIA of uninjured contralateral knees; (2) Peak knee flexion moment (balanced by net quadriceps moment) during walking is negatively correlated with the PLIA in ACL-reconstructed knees. The PLIA of 24 ACL-reconstructed and contralateral knees were measured using MRI, and peak knee flexion moments during walking were measured. Results showed that the PLIA of ACL-reconstructed (22.9 ± 4.4°) knees was not significantly smaller (p = 0.09, power = 0.99) than the PLIA of contralateral (24.1 ± 4.8°) knees. Peak knee flexion moment was not correlated with the PLIA following ACL reconstruction (R² = 0.016, power = 0.99). However, the magnitude of the knee flexion moment remained significantly lower in ACL-reconstructed knees. In summary, this study has shown that the PLIA of ACL-reconstructed knees returned to normal and that patients no longer adapt their gait in response to the PLIA, though quadriceps function did not return to normal levels. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 730–735, 2009     

Adaptive patterns of movement during stair climbing in patients with knee osteoarthritis

The purpose of this study was to determine if there is a distinctive characteristic in the pattern of movement (forward trunk lean to reduce demand on the quadriceps muscle) during stair climbing in patients with knee osteoarthritis (OA) that is associated with the severity of the disease. Twenty‐three patients with radiographically diagnosed knee OA and 20 physically active adults performed stair ascending trials without support at their self‐selected speed. Standard gait analysis was used to calculate three‐dimensional lower extremity joint kinematics and kinetics. Forward trunk lean, or trunk flexion, was defined as the sagittal plane projection of the angle between a line connecting the midpoint of the trans‐acromion line and the midpoint of the trans‐iliac crest line and the global vertical axis. Patients with more severe knee OA (KL ≥ 3) had greater forward trunk lean (+6.3°, p = 0.045) and lower knee net quadriceps moments (?35.2%, p = 0.001) than controls. In more severe patients, the forward trunk lean was correlated with a reduction in the net quadriceps moment during stair climbing (R² = 0.590, p = 0.006). The results of this study identified a distinctive compensatory pattern of movement to reduce the quadriceps demand during stair climbing in patients with more severe knee OA by increasing forward trunk lean. Assessing forward trunk lean during stair climbing may be a useful functional marker for evaluating osteoarthritis status and quadriceps function that appears to be a more sensitive indicator of disease severity than perceived pain. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:325–329, 2009     

基于7次跨膜受体的药物发现基本方法——细胞检测

随着检测技术进步,含7个跨膜α螺旋结构的受体性质已渐为人们所了解。7次跨膜（7TM）受体不仅具有开关功能,更类似于信息微处理器;特定配体只能参与特定受体介导的部分信号机制,这就为药物发现开拓了一个新领域。为进一步发现7TM受体与配体间的新行为并量化评价药物对这一复杂系统的作用效能,进而指导药物化学研究,药理学检测已成为关注焦点。本文阐述从还原重组体到整体系统测定方法的回归,讨论药物效价与评价其效应的特定检测方法间的联系,强调新的检测方法在药物发现过程中的价值。     

A relationship between stem orientation and function following total hip arthroplasty

A retrospective gait analysis of patients with cemented Charnley-Mueller total hip arthroplasties was conducted to determine if functional differences exist between patients with femoral stems placed in varus and valgus orientations. Twenty patients and ten normals were studied using gait analysis to quantify joint motion and moments during level walking. In addition, a radiographic analysis of stem placement and mechanics of the reconstructed hip was performed on the total hip patients. All patients selected for the study had excellent clinical results on the basis of a score of 95 or better on the Harris hip rating form. The patients were divided into two subgroupings on the basis of stem orientation. A valgus group was defined as having a valgus stem orientation relative to the femoral shaft, with the femoral head-shaft offset shortened by 5 mm or greater compared to the contralateral unoperated hip, while the varus group was defined on the basis of having a varus stem orientation relative to the femoral shaft, with the femoral head-shaft offset restored to normal or greater than normal. A difference in gait was found between the varus and valgus patient groupings. The varus group had abnormal gait characteristics in the range of hip motion, the flexion-extension moments at the hip, and stride length. The patients in the valgus group had statistically normal gait. The differences in the gait characteristics were interpreted as an attempt to alter forces on the hip joint for patients in the varus group. These alterations were possibly an early indication of a subtle adaptation in patients with varus-placed femoral stems since, historically, a greater percentage of the patients in this configuration, retrospectively, go on to mechanical failures.(ABSTRACT TRUNCATED AT 250 WORDS)