Antihypertensive Combination Therapy: Optimizing Blood Pressure Control and Cardiovascular Risk Reduction

Treating hypertension reduces the rates of myocardial infarction, stroke, and renal disease; however, clinical trial experience suggests that monotherapy is not likely to be successful for achieving goal blood pressure (BP) levels in many hypertensive patients. In multiple recent clinical trials including various subsets of hypertensive patients, the achievement of BP goal has typically required the combination of 2 or more medications, particularly in patients with BP levels >160/100 mm Hg. When initiating combination therapy for hypertension, careful consideration must be given to the choice of medication. Clinical trial evidence has shown the efficacy of various combinations of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, and diuretics in reducing BP and cardiovascular risk. Ongoing trials should provide additional guidance on the optimal choice of combination regimens in specific clinical settings.     

Response of lumbar paraspinal muscles spindles is greater to spinal manipulative loading compared with slower loading under length control.

BACKGROUND CONTEXT: Spinal manipulation (SM) is a form of manual therapy used clinically to treat patients with low back and neck pain. The most common form of this maneuver is characterized as a high-velocity (duration <150 ms), low-amplitude (segmental translation <2 mm, rotation <4 degrees , and applied force 220-889 N) impulse thrust (high-velocity, low-amplitude spinal manipulation [HVLA-SM]). Clinical skill in applying an HVLA-SM lies in the practitioner's ability to control the duration and magnitude of the load (ie, the rate of loading), the direction in which the load is applied, and the contact point at which the load is applied. Control over its mechanical delivery is presumably related to its clinical effects. Biomechanical changes evoked by an HVLA-SM are thought to have physiological consequences caused, at least in part, by changes in sensory signaling from paraspinal tissues. PURPOSE: If activation of afferent pathways does contribute to the effects of an HVLA-SM, it seems reasonable to anticipate that neural discharge might increase or decrease in a nonlinear fashion as the thrust duration approaches a threshold value. We hypothesized that the relationship between the duration of an impulsive thrust to a vertebra and paraspinal muscle spindle discharge would be nonlinear with an inflection near the duration of an HVLA-SM delivered clinically (<150 ms). In addition, we anticipated that muscle spindle discharge would be more sensitive to larger amplitude thrusts. STUDY DESIGN/SETTING: A neurophysiological study of spinal manipulation using the lumbar spine of a feline model. METHODS: Impulse thrusts (duration: 12.5, 25, 50, 100, 200, and 400 ms; amplitude 1 or 2 mm posterior to anterior) were applied to the spinous process of the L6 vertebra of deeply anesthetized cats while recording single unit activity from dorsal root filaments of muscle spindle afferents innervating the lumbar paraspinal muscles. A feedback motor was used in displacement control mode to deliver the impulse thrusts. The motor's drive arm was securely attached to the L6 spinous process via a forceps. RESULTS: As thrust duration became shorter, the discharge of the lumbar paraspinal muscle spindles increased in a curvilinear fashion. A concave-up inflection occurred near the 100-ms duration eliciting both a higher frequency discharge compared with the longer durations and a substantially faster rate of change as thrust duration was shortened. This pattern was evident in paraspinal afferents with receptive fields both close and far from the midline. Paradoxically, spindle afferents were almost twice as sensitive to the 1-mm compared with the 2-mm amplitude thrust (6.2 vs. 3.3 spikes/s/mm/s). This latter finding may be related to the small versus large signal range properties of muscle spindles. CONCLUSIONS: The results indicate that the duration and amplitude of a spinal manipulation elicit a pattern of discharge from paraspinal muscle spindles different from slower mechanical inputs. Clinically, these parameters may be important determinants of an HVLA-SM's therapeutic benefit.     

Color Stability of Dry Earth Pigmented Maxillofacial Silicone A-2186 Subjected to Microwave Energy Exposure

PURPOSE: The purpose of this study was to measure spectrophotometrically the color stability of pigmented A-2186 silicone maxillofacial elastomer with 10% by volume of titanium white dry earth opacifier before and after exposure to microwave energy over a simulated 1.5-year period of microwave sterilization. Materials AND METHODS: A-2186 silicone elastomer opacified with titanium white dry earth pigment, pigmented with 5 cosmetic dry earth pigment colors [no pigment (control) group (Pc), red (Pr), yellow ochre (Py), burnt sienna (Po), and a mixture of Pr + Py + Po color group (P3)], was used in this study. Each of the 5 experimental groups consisted of 5 specimens. All specimens were placed in a 250 ml glass beaker filled with 150 ml of water (replenished for each microwave exposure). An exposure of 6 minutes was used 18 times (simulating 1.5 years of microwave sterilization with one 6 minute exposure monthly). Reflectance values were measured by spectrophotometer. Three- and two-way analyses of variance with repeated measures were performed for the color difference (DeltaE*) with the factors of group/color/months, and group/months, respectively. Means were compared by Tukey Honest Significant Difference (HSD) multiple range test calculated at the 0.05 level of significance using SPSS. RESULTS: The trained human eye can detect color changes (DeltaE*) greater than 1.0. Most DeltaE* values of the red pigment group at all intervals and the mixed pigment group at 15- and 18- month intervals increased significantly greater than 1.0 (p < 0.001) compared with the control group. Yellow and burnt sienna groups remained the most color stable over time with DeltaE* values below 0.35. CONCLUSIONS: Lack of color stability of red dry earth pigmented A-2186 silicone maxillofacial elastomers was clinically significant after 12-month exposure to microwave energy as compared with yellow, burnt sienna, and opacified A-2186 dry earth pigments.     

子宫腺肌症病变中雌激素、孕激素、癌基因、凋亡抑制基因的表达研究

目的 研究雌激素（ER）、孕激素（PR）及癌基因（cerbB-2）、凋亡抑制基因（Bcl-2）在子宫腺肌症病变中的表达和子宫腺肌症发病的相关性。方法 用免疫组化方法检测40例子宫腺肌症病变组织中ER及其他生物学指标的表达。结果 ER、PR与CerbB．2、Bcl-2在子宫腺肌症病变中均有不同程度的阳性表达，子宫肌层异位内膜ER阳性表达率97．5％，PR阳性率97．5％，cerbB-2阳性率82．5％，Bcl-2阳性率62．5％。在位内膜和异位内膜ER、PR均呈阳性，阳性率比较差异无统计学意义（P〉0．05）。异位内膜cerbB-2的强阳性率高于在位内膜，差异有统计学意义（P〈0．05）。ER、PR与cerbB-2、Bcl-2阳性率相比具有相关性（P〈0．05）。结论 ER、PR与cerbB．2、Bcl-2在异位内膜高表达，提示这些生物学指标在子宫腺肌症发生发展中发挥作用。