Pharmaco-economic aspects of the treatment of hypertension

The Periotron is an instrument designed to quantify submicrolitre volumes of fluid sampled on a filter paper strip. To date 3 models have been manufactured: the Periotron 600 (1976), the Periotron 6000 (1983) and more recently the Periotron 8000 (1995). This paper investigated for the first time the calibration characteristics and reliability of the Periotron 8000. The fluids under investigation were: de-ionised water, human serum, fetal bovine serum and an ultrafiltrate of fetal bovine serum. Quantitative analysis was studied by recording a series of Periotron readings over a volume range of 0-1.0 microliters for each fluid. The average of 5 Periotron values for each particular fluid was then plotted versus the respective fluid volume. Qualitative changes in fluid composition versus Periotron Scores were also analysed. Volume conversion for Periotron scores using both Periotron MLCONVRT software and a best fit equation selected from TableCurve 2D software compared well. The results of this study revealed that: 1) differences in calibration fluid composition (e.g. protein content) are reflected in the Periotron scores; 2) positioning of filter paper strip between the jaws of the Periotron should be standardised, 3) calibration of the Periotron 8000 seems to be consistent over a 1-wk interval.     

Multiple myeloma: new aspects of biology and treatment

Recently, considerable progress has been made in understanding of the biology and treatment of multiple myeloma. Molecular genetic abnormalities such as bcl-2,c-myc, ras, p53, and Rb genes have been identified in this disease and are related to a poor prognosis. Cytokine studies have revealed that interleukin-6 is a potent growth factor for myeloma cells and is also responsible for the progressive bone resorption together with interleukin-1 beta and tumor necrosis factor. Myeloablative chemotherapy followed by allogeneic or autologous hematopoietic stem cell transplantation has increased the incidence of complete remission. However, relapses are still observed because of drug resistance of tumor cells. Immunotherapeutic approaches targeting to cell surface antigens and interleukin-6 signals are being developed to further eliminate myeloma cells. Translating new biological advances into treatment protocols is essential to improve the prognosis of multiple myeloma.     

Behavioral and environmental aspects of hypertension

Relationships of behavioral and environmental influences on the development and maintenance of hypertension have been reviewed. The evidence for such influences arises from studies in five areas, namely, retrospective correlations between emotional events and hypertensive disease; acute changes in blood pressure with stress in animals and man; chronic blood pressure change following stress in animals and man; changes in blood pressure produced by behavioral modifications; and the personality patterns and particular behaviors of hypertensive subjects. Data from these studies have been briefly but critically reviewed with emphasis on the interreactive nature of the environmental, behavioral, genetic and other biological factors which eventuate in hypertension. It is emphasized that the issue for the future is not whether behavioral factors play any role in hypertension but rather to what extent, under what circumstances, and in which individuals behavioral factors are acting as important pressor stimuli in the overall homeostatic distortions that result in hypertension.     

厄贝沙坦氢氯噻嗪复方制剂治疗原发性高血压有效性及安全性的Meta分析

目的:利用Meta分析方法探讨厄贝沙坦氢氯噻嗪复方制剂治疗原发性高血压的有效性及安全性,为其临床应用提供依据.方法:计算机检索Cochrane图书馆临床对照试验资料库(2010年第03期)、Ovid-medline全文数据库(1966-2010.09)、PubMed数据库(1948-2010.09)、EMBASE数据库(1966-2010.09)、中国学术文献总库(CNKI)(1979-2010.09)、万方数字化期刊库(1981-2010.09)及维普数据库(VIP) (1989-2010.09),手工检索相关文献,按纳入与排除标准选择试验、评价质量,提取资料,并用RevMan 4.2软件对数据进行Meta分析.结果:共初检出516篇文献,经筛选最终纳入5篇6项关于厄贝沙坦氢氯噻嗪治疗原发性高血压的随机双盲对照研究.有效性:χ2=7.50,df=5,P=0.19,Z=7.23(P<0.00001),合并OR=2.26,95%CI [1.81,2.82];安全性:χ2=7.82,df=5,P=0.17,Z=1.11(P=0.27),合并OR=0.87,95%CI [0.68,1.11].结论:厄贝沙坦氢氯噻嗪复方制剂治疗原发性高血压与对照组比较具有较高的有效性及相似的安全性.     

Alpha 1-blocker combination therapy for hypertension

Combination therapy is a cost-effective and rational approach to treatment of severe hypertension and of mild to moderate hypertension that is refractory to monotherapy. The method has several advantages, most notably improved tolerability and enhanced antihypertensive efficacy. Long-term prospective studies are needed to confirm that such agents as calcium channel blockers, ACE inhibitors, and alpha 1 blockers reduce end-organ damage more effectively than do older antihypertensive drugs. However, scientific evidence strongly suggests that reducing risk factors for end-organ damage reduces heart, brain, kidney, and large-artery injury. Alpha 1 blockers appear to be a particularly suitable choice for use in combination regimens. The only class of agents that should be avoided in combination with alpha 1 blockers is central alpha agonists; all other agents act in an additive or synergistic fashion. Unlike diuretics and beta blockers, alpha 1 blockers do not adversely affect serum lipid, glucose, or insulin levels. In fact, alpha 1 blockers may improve these measurements and also counteract the adverse effects of other antihypertensive agents on them. Alpha1-blocker therapy may bring about regression of LVH, and it does not have deleterious effects on disorders that often coexist with hypertension (e.g., gout, chronic obstructive lung disease, peripheral ischemia).     

当代教学目标分类理论研究的新进展

在课堂教学中,为了把教学目的落实到教学过程中去,必须把教学目的具体化、细拟化和操作化,建立教学目标体系,即教学目标分类.教学目标分类是指运用分类学的理论,把教学目的按照由简单到复杂、从低级到高级连续递增的形式进行有序的排列组合,使之系列化.教学目标体系应该是一套具体可测的、行为操作化的、看得见、摸得着的目标,这对于现实教学的目的和进行课堂教学质量评价具有十分重要的意义.自20世纪50年代以来,人们对教学目标分类问题进行了系统、深入的研究,提出了几种重要的教学目标分类理论.     

Low-dose reserpine/thiazide combination in first-line treatment of hypertension: efficacy and safety compared to an ACE inhibitor

The concept of initiating treatment of mild-to-moderate hypertension with a low-dose combination of reserpine and the thiazide clopamide in comparison to monotherapy with an ACE inhibitor was investigated. A total of 127 adult outpatients with diastolic blood pressure between 100 and 114 mmHg were randomized into this double-blind, parallel group study. After a 2-week wash-out period and a subsequent 2-week placebo run-in period, they were allocated to once-daily treatment with 0.1 mg reserpine plus 5 mg clopamide (R/C), or 5 mg enalapril. If diastolic blood pressure was not normalized after 3 weeks of therapy (i.e. DBP < 90 mmHg), the dosage was doubled from week 4 to 6. The primary efficacy variables were the change from baseline in mean sitting diastolic and systolic blood pressure (DBP/SBP) after 3 weeks of therapy. Secondary variables included the change in DBP and SBP after 6 weeks of therapy, the BP normalization rates at 3 and 6 weeks and, concerning tolerability, the rates of adverse events after 6 weeks of therapy. An intent-to-treat analysis was performed. The reserpine/ clopamide and enalapril groups did not differ with regard to demographic and baseline characteristics (mean age 57 or 58 years, respectively; 63% or 56% males, respectively; mean SBP/DBP after the 2-week placebo period = 156 mmHg/104 mmHg in both groups). After 3 weeks of treatment with one capsule daily, mean SBP/DBP reduction from baseline (24 h after last medication intake) in the R/C combination group was -19.6/ -17.0 mmHg, in the enalapril group -6.1/ -9.5 mmHg (between-group comparison: 2p < 0.01 for both parameters). The normalization rates for DBP (< 90 mmHg) were 64.1% (R/C) and 28.6% (enalapril) (2p < 0.01). Adverse events that were considered possibly or definitely drug-related by the investigator were noted in 11 patients (17.2%) in the R/C group and in 9 patients (14.3%) in the enalapril group (NS). Two patients in the enalapril group discontinued the study prematurely due to adverse events (cough; skin eruption). In the treatment of mild-to-moderate hypertension, a low-dose combination of reserpine and clopamide once a day is considerably more effective than, and as tolerable as, 5-10 mg of enalapril once a day. These findings suggest that treatment with a combination of different antihypertensives with different modes of action in low doses is a rational alternative to conventional monotherapy in the first-line treatment of hypertension. Besides, the "old" reserpine-diuretic regimen also in these days appears to be a rational alternative to "modern" monotherapies.     

NIDDM: new aspects of management

Patients over age 40 should be made aware of the triad of risk factors for the disease and taught to recognize common signs and symptoms. Those with high-risk profiles should be tested regularly and counseled regarding preventive and therapeutic strategies. For obese patients whose weight cannot be brought under control with diet and exercise alone, a trial of anorectic agents should be considered.     

The TEAM study--a study of the effectiveness and tolerance of treatment of essential hypertension with a fixed combination of trandolapril and verapamil

In the years 1988 to 1995 among 1355 cattle examined in the frame of iodine deficiency studies in the Czech Republic 404 animals (30%) showed congenital struma. Clinical and postmortal findings are described. A monitoring of iodine content in milk showed lower values in herds with struma prevalence. The insufficient supply of iodine in these animals results from low iodine content of feed or from the goitrogenic influence of nitrate in drinking water or high content of crucifera in feed or other stress factors. An increased iodination of mineral mix in feed is highly recommended.     

The rationale for combination versus single-entity therapy in hypertension

The rationale behind combination therapy relates to the fact that when two different classes of agents are combined, they may provide complementary, additive, or synergistic antihypertensive effects through different mechanisms. Lower doses of two drugs, which provide blood pressure reduction similar to higher doses of one drug, may enhance tolerability and improve compliance. Investigative efforts have been undertaken to explore fixed-dose combinations of drugs that do not include diuretics. The first nondiuretic fixed-dose combinations are an angiotensin-converting enzyme (ACE) inhibitor-calcium antagonist combination or a beta-blocker-calcium antagonist combination. The rationale for an ACE inhibitor-calcium antagonist combination is based on the fact that both drugs reduce vasoconstriction through different mechanisms. The ACE inhibitor largely attenuates vasoconstriction through augmentation of vasodilatory kinins and reduction of the vasoconstrictive effect of angiotensin II, whereas the calcium antagonists, through attenuating the transmembrane flux of calcium, inhibit calcium-mediated electromechanical coupling in contractile tissue in response to numerous stimuli. Moreover, both classes of drugs facilitate salt and water excretion by the kidney through different mechanisms. The ACE inhibitor restores the renal-adrenal response to salt loading, whereas the calcium antagonist possesses intrinsic natriuretic properties through poorly described mechanisms of inhibiting renal tubular salt and water reabsorption. The combination of a beta-blocker and dihydropyridine calcium antagonist is logical due to the different antihypertensive mechanisms of these drugs without risk of cardiac conduction abnormalities. There is evidence in clinical trials that ACE inhibitors may offset one of the major side effects associated with calcium antagonist therapy: pedal edema. Although the studies are small and the observations subjective, there is consistent evidence that the combination may provide an opportunity to reduce the likelihood of this common clinical problem. There is also evidence of reduced calcium antagonist-associated constipation and headache with this type of drug combination, likely because lower doses of this agent are used in combination with ACE inhibitors. However, there is no published evidence that calcium antagonists reduce the cough associated with the ACE inhibitor.