Randomised comparison of methyldopa and oxprenolol for treatment of hypertension in pregnancy.

Fifty-three pregnant women with moderately severe hypertension were randomly allocated to treatment with methyldopa or oxprenolol. There were no significant differences between the groups in age, height, weight, parity, or stage of gestation at the start of treatment. The outcome of pregnancy was better in the group treated with oxprenolol, with greater maternal plasma volume expansion and placental and fetal growth. No intrauterine deaths occurred in either group, and antepartum fetal distress, detected by oxytocin challenge testing, was evident in only one patient, who received methyldopa. This infant, and one other in the methyldopa group, died in the neonatal period. No neonatal deaths occurred in the oxprenolol-treated group. Even in this small number of patients these results were considerably better than those in untreated women with hypertension of similar severity. Apgar scores in both groups were equivalent at birth, while blood sugar concentrations were higher in the oxprenolol group. Oxprenolol appears to be safe and effective in controlling hypertension during pregnancy. There was no evidence of harmful effects on the fetus, and oxprenolol may offer a selective advantage over methyldopa for fetal growth and wellbeing in utero.     

Randomised controlled comparative study of methyldopa and oxprenolol in treatment of hypertension in pregnancy.

One hundred pregnant women with hypertension (defined as diastolic blood pressure at or above 95 mm Hg) were allocated at random to treatment with methyldopa or oxprenolol and were compared with nonhypertensive controls matched according to parity and gestation at delivery. The patients were also stratified into those entering the study early (before 32 weeks'' gestation) and those entering late (after 32 weeks'' gestation). Although there were no differences in diastolic blood pressure between the hypertensive groups before or during treatment, in the early entry group the systolic blood pressure at entry of those allocated to oxprenolol was significantly higher than that of those receiving methyldopa; this difference remained throughout the treatment period. Also in the early entry group further increments of drug treatment were required to control blood pressure of patients receiving oxprenolol than in those receiving methyldopa. The eventual fetal outcome for all patients treated with methyldopa was the same as that for those treated with oxprenolol; birth weight, placental weight, head circumference, and Apgar score were not significantly different and there were no stillbirths in either group.     

硝酸甘油联合甲基多巴治疗重度子痫前期的效果研究

目的:探讨硝酸甘油联合甲基多巴治疗重度子痫前期的临床效果及对围产结局的影响。方法:选取2015年5月～2018年6月我院收治的重度子痫前期患者81例作为研究对象,根据患者入院先后顺序分为对照组(40例)和观察组(41例),对照组给予常规治疗,观察组在对照组的基础上给予硝酸甘油联合甲基多巴治疗。比较两组患者的临床治疗效果、治疗前后平均动脉压(MAP)、24h尿蛋白(24 pro)和心率(HR)水平的变化及围产结局。结果:治疗后,观察组患者的总有效率显著高于对照组(95.12%vs. 80%,P0.05),两组MAP、24 pro和HR水平均较治疗前显著下降,且观察组的MAP和24 pro水平显著低于对照组(P0.05);观察组患者的产后出血、胎盘早剥、胎儿窘迫和新生儿窒息的发生率显著低于对照组,自然分娩率显著高于对照组(P0.05),两组的低体重儿的发生率相比无统计学差异(P0.05)。结论:硝酸甘油联合甲基多巴可有效降低重度子痫前期患者的血压和24 pro水平,提高自然分娩率,改善围产结局,显著提高临床效果。     

甲基多巴联合酚妥拉明治疗妊娠期高血压的临床疗效及安全性研究

目的:研究甲基多巴联合酚妥拉明治疗妊娠期高血压的临床疗效及安全性。方法:选择2015年1月～2017年12月我院收治的妊娠期高血压疾病患者210例,并将其随机分为两组。对照组静脉滴注酚妥拉明治疗,每次20 mg,每天1次;观察组联合口服甲基多巴,每次250 mg,每天3次。比较两组的治疗有效率,妊娠情况及治疗前后的收缩压(SBP)、平均动脉压、舒张压(DBP)和尿素氮(BUN)、血肌酐(Cr)、β2微球蛋白(β2-MG)和尿微量清蛋白(MA)水平的变化。结果:治疗后,观察组的有效率明显高于对照组(P0.05);观察组的产后出血、胎盘剥落、子痫前期、羊水栓塞先兆以及剖宫产发生率均明显低于对照组(P0.05)。两组治疗后的SBP、MAP和DBP均较治疗前明显降低(P0.05),且观察组SBP、MAP和DBP明显低于对照组(P0.05)。两组治疗前后的Cr、BUN水平相比均无明显的差异(P0.05),两组治疗后的血清β2-MG和MA水平均较治疗前明显降低(P0.05),且观察组以上指标明显低于对照组(P0.05)。两组的不良反应发生情况相比差异无统计学意义(P0.05)。结论:甲基多巴联合酚妥拉明治疗妊娠期高血压的临床效果明显优于单用酚妥拉明治疗,其可以更有效控制血压,改善患者肾功能,且安全性较高。     

The Long-Term Effectiveness of Methyldopa in Hypertension

A trial of methyldopa in hypertension was conducted in 60 patients for a mean time of 9.4 months. Initially, four different dosages of methyldopa were studied and blood pressure was significantly lowered in the supine and standing positions. Standing blood pressure was significantly reduced more than supine. An average of 5.2 visits passed before maintenance blood pressure was obtained. There was no significent evidence of deterioration during the duration of this study. Side effects were mild. Only two patients voluntarily requested discontinuance of this study. Tolerance to the drug occurred and approximately 50 per cent of the patients no longer had a significant blood pressure reduction to methyldopa alone by the end of the study. Methyldopa appears to be a significant addition to the drug therapy of hypertension.     

Atenolol,methyldopa, and chlorthalidone in moderate hypertension.

Combined treatment with low doses of different drugs is widely used for moderate hypertension. The effects of atenolol and methyldopa at two dose levels and in combination at the lower doses were studied in patients with moderate hypertension on continuous treatment with moderate hypertension on continuous treatment with chlorthalidone. The mean reduction in standing blood pressures obtained with atenolol 150 and 300 mg/day was about 27/17 mm Hg and with methyldopa 750 and 1500 mg/day about 28/14 mm Hg. Combined treatment with atenolol 150 mg/day and methyldopa 750 mg/day for four weeks resulted in a reduction of 38/25 mm Hg. No difference was observed between the two doses of methyldopa. The lower dose of atenolol was better than the lower dose of methyldopa in reducing lying and standing diastolic blood pressures. These findings show that in patients on continuous treatment with chlorthalidone the addition of atenolol alone or methyldopa alone or of atenolol and methyldopa in combination is effective in the treatment of moderate hypertension.     

Reduced Fetal Telomere Length in Gestational Diabetes

Gestational diabetes mellitus (GDM) is an important complication of pregnancy that poses significant threats to women and their offspring. Telomere length shortens as cellular damage increases and is associated with metabolic diseases. Telomere length in fetal leucocytes was determined in 82 infants of women with GDM (N = 82) and 65 normal pregnant women (N = 65). Women with preeclampsia (N = 45) and gestational hypertension (N = 23) were also studied. In the GDM group, telomere length was significantly shorter than normal pregnancy (P = 0.028), but there were no significant differences in fetal telomere length between preeclampsia and normal pregnancy (P = 0.841) and between gestational hypertension and normal pregnancy (P = 0.561). Regression analysis revealed that fetal telomere length was significantly associated with intrauterine exposure to GDM (P = 0.027 after adjustment for maternal age, gestational age at delivery, birth weight and fetal gender). Shortened telomere length may increase the risk of metabolic diseases in adulthood of GDM offspring.     

The effect of oral glucose tolerance testing on changes in arterial stiffness and blood pressure in elderly women with hypertension and relationships between the stage of diabetes and physical fitness levels

[Purpose] The purpose of this study was to assess changes in blood glucose level, blood pressure, and arterial stiffness after a 75 g oral glucose tolerance test (OGTT) in elderly women aged over 65 years with hypertension and either normal glycemic control, impaired fasting glucose tolerance, or diabetes mellitus. We also wished to investigate the relationship between stages of diabetes and physical fitness.[Methods] A total of 24 elderly women with hypertension were assigned to a control group (CON; n=7), impaired fasting glucose group (IFG; n=9), and diabetes mellitus group (DM; n=8). In each group, blood glucose level, brachial ankle pulse wave velocity (PWV), and blood pressure were measured at baseline as well as 60 and 120 minutes after a 75 g OGTT. Physical fitness factors such as hand grip strength, balance test, 4 m gait speed test, chair stand test, short physical performance battery, and 6-minute walking test were subsequently assessed.[Results] In all three groups, blood glucose levels were significantly increased at 60 and 120 minutes after a 75 g OGTT. In the DM group, blood glucose levels were significantly higher before and after a 75 g OGTT than in the CON group. In the CON group, PWV was significantly increased at 60 minutes after a 75 g OGTT; however, there were no changes in other groups after glucose ingestion. In the CON group, systolic and diastolic blood pressures were significantly decreased at 60 and 120 minutes after a 75 g OGTT compared to baseline. However, there was no change in blood pressure after ingestion in the DM group. The IFG group had greater grip strength than the CON group; however, there were no differences in other variables between the groups.[Conclusion] After a 75 g OGTT, elderly women with hypertension and diabetes maintain higher blood glucose levels compared to those with hypertension alone. Unlike elderly women with hypertension alone, those with hypertension and diabetes did not show changes in arterial stiffness and blood pressure after a 75 g OGTT. Therefore, elderly women with hypertension and diabetes may not be able to control their blood vessels following a 75 g OGTT due to impaired vascular endothelial function. Moreover, there was no association between diabetes stage and physical fitness in elderly women with hypertension.     

Controlled trial of speech therapy versus oxprenolol for stammering.

In a controlled trial of treatment for stammering under stress oxprenolol (40 mg) compared with placebo was assessed in a double-blind manner over two days, six weeks apart, in 31 stammerers before and after speech therapy. The trial design also allowed six weeks of intensive speech therapy, using a slowed-speech and relaxation technique, to be compared with not treatment and assessed single-blind. Oxprenolol produced a significant fall in pulse rate and systolic blood pressure but no overall change in performance either before or after speech therapy. Intensive speech therapy produced a highly significant improvement in the global performance of untrained subjects (p less than 0.001) and a significant reduction in the number (p less than 0.001) and duration (p less than 0.001) of blocks. Maintenance speech therapy tended to produce further improvement in trained subjects. Speech therapy is apparently an effective treatment for stammering, whereas oxprenolol appears to be of no value when given routinely; oxprenolol may be of value, however, in very stressful conditions.     

Approach to drug therapy for hypertension.

Prevention of complications of hypertension requires the lowering of blood pressure. The therapeutic goal is to achieve and maintain a diastolic pressure of less than 90 mm Hg with minimal adverse effects. The treatment of patients with established diastolic blood pressures between 90 and 104 mm Hg (determined from three separate readings) should be individualized; general measures such as weight loss and salt restriction should be tried first as an alternative to drug therapy. Patients with diastolic pressure in excess of 104 mm Hg should be treated with antihypertensive drugs; the first step should be the use of a thiazide diuretic in addition to general measures. Patients with diastolic pressures of 90 to 115 mm Hg may require the addition of a beta-adrenergic-receptor antagonist, methyldopa or clonidine if the therapeutic goal is not achieved; rarely they require the further addition of hydralazine or prazosin. Patients with diastolic pressures of 116 to 129 mm Hg usually require initially both a thiazide diuretic and a beta-blocker, methyldopa or clonidine; if the therapeutic goal is not achieved, hydralazine or prazosin is added, and if a further hypotensive effect is required guanethidine can be added. Patients with severe hypertension (diastolic pressures greater than 130 mm Hg) may require urgent treatment with combinations of drugs of all three levels. Emphasis should be placed on individualized therapy and patient compliance in the assessment of therapeutic failures. These "step-care" guidlines represent a framework for antihypertensive therapy devised from information available in 1977. It is not a rigid scheme and should be adjusted to the individual patient to ensure as normal a life as possible.     

Effect of antihypertensive therapy with alpha methyldopa on levels of angiogenic factors in pregnancies with hypertensive disorders

Background

Antihypertensive drugs are believed to lower blood pressure in pre-eclampsia by direct or central vasodilatory mechanisms. However, they could also act by decreasing production of anti-angiogenic proteins involved in the pathophysiology of hypertension and proteinuria in pre-eclampsia (PE). The aim of our study was to evaluate the impact of antihypertensive therapy with alpha methyldopa on maternal circulating levels and placental production of soluble fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin (sEng), vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) in hypertensive disorders of pregnancy.

Methodology/Principal Findings

In a study conducted at University College Hospital and the Homerton University Hospital in London, we recruited 51 women with PE, 29 with gestational hypertension (GH), and 80 matched normotensive controls. Eight (16%) of the women with PE had severe disease. Placental samples were obtained from a further 48 women (14 PE, 10 GH and 24 matched controls). Serum levels of angiogenic factors were measured before and 24–48 hours after commencing antihypertensive therapy with alpha methyldopa for clinical indications. The same parameters were measured in placental extracts. In both PE (P<0.0001) and GH (P<0.05), serum sFlt-1 was increased and PlGF reduced at all gestations (P<0.001) compared to controls. Serum sEng levels were also increased in PE. Placental concentration of sFlt-1 and sEng was significantly higher in women with PE compared to controls and women with GH (P<0.0001). The concentration of PlGF was significantly lower in the placental tissue of women with PE compared to GH (P = 0.008). Antihypertensive treatment was associated with a significant fall in serum and placental content of sFlt1 and sEng in PE only.

Conclusions

Our data suggest that alpha methyldopa may have a specific effect on placental and/or endothelial cell function in pre-eclampsia patients, altering angiogenic proteins.     

干预治疗对TPOAb阴性亚甲减孕妇妊娠结局的影响

目的:探讨干预治疗对不同TSH水平的妊娠期亚临床甲减合并甲状腺过氧化物酶(TPOAb)阴性孕妇妊娠结局的影响。方法:回顾性分析2016年1月1日至2016年12月31日在青岛大学附属医院产科分娩孕妇诊断为亚临床甲减且TPOAb阴性的孕妇不良妊娠结局的发生率,根据2011年(S1标准)及2017年(S2标准)美国甲状腺协会(ATA)指南对妊娠合并亚临床甲减推荐诊断的TSH水平不同分组,A组(4 m IU/LTSH10.0 m IU/L)131例,B组(TSH4 m IU/L,在T1期TSH2.5 m IU/L,T2、T3期TSH3.0 m IU/L)326例,根据是否接受左甲状腺素钠片(商品名:优甲乐)治疗,分为治疗组(295例)、未治疗组(194例),同时选取TPOAb阴性且甲状腺功能正常的孕妇(306例)作为对照组。结果:(1)依据S1、S2诊断标准,妊娠合并亚临床甲减的发生率分别为13.57%、3.6%,治疗率分别为39.67%、51.34%,不同诊断标准间比较差异具有统计学意义(P0.05)。(2)A组孕妇中,未治疗组妊娠期高血压疾病、妊娠期糖尿病、妊娠期贫血、流产、早产、胎儿窘迫的发生率均高于治疗组及对照组,差异具有统计学意义(P0.05),而治疗组与对照组比较差异无统计学意义(P0.05)。未治疗组胎盘早剥、胎膜早破、胎儿畸形、低体重儿的发生率虽高于治疗组及对照组,但两两比较差异均无统计学意义(P0.05)。(3)B组孕妇未治疗组妊娠期高血压疾病、妊娠期糖尿病、妊娠期贫血、流产、早产、胎儿窘迫、胎盘早剥、胎膜早破、胎儿畸形、低体重儿的发生率虽高于治疗组及对照组,三组及两两比较差异无统计学意义(P0.05)。结论:对于青岛地区TPOAb阴性的妊娠期亚临床甲减孕妇,4.0 m IU/LTSH10.0 m IU/L时,左甲状腺素钠片治疗能明显改善其不良妊娠结局。     

Effect of methyldopa treatment on cardiac function and myocardial blood flow in mongrel dogs.

Administration of methyldopa (100 mg/kg, orally twice daily for a period of 3 days) to mongrel dogs produced significant reductions in blood pressure and heart rate. The hypotensive effect of the drug was due to a reduction in peripheral resistance. Methyldopa treatment also produced a significant decrease in coronary vascular resistance. Studies on the left ventricular function indicated that treatment with methyldopa does not compromise the ability of the myocardium to respond to an increased work load. Thus, the beneficial effect of this agent on the myocardial circulation, together with its lack of any detrimental effect on the cardiac function suggest that methyldopa may be an effective agent for the control of hypertension.     

Value of bromocriptine in unexplained primary infertility: a double-blind controlled trial.

In a double-blind controlled study, 47 women with unexplained primary infertility were allocated at random to treatment with either bromocriptine 2.5 mg twice daily (24 patients) or placebo (23). Both groups showed a fall in serum prolactin concentrations but the reduction was much greater in the bromocriptine-treated group. Neither group showed a change in serum oestrogen or progesterone concentrations. Bromocriptine significantly reduced the duration of the follicular phase of the menstrual cycle but had no effect on the luteal phase. Five women conceived during treatment with placebo and seven during treatment with bromocriptine, but analysis of the cumulative conception rates showed no significant difference between the groups. The women who conceived were significantly younger and had a significantly shorter history of infertility than the women who did not conceive, but subtracting the number of years of infertility from age eliminated this difference. The results show that bromocriptine in the dose and duration of administration used in the trial is of no value in unexplained primary infertility.     

Raised Serum IgG Levels in Hypertension

Serum IgG levels were significantly higher in 118 severely hypertensive patients compared with a group of 163 normotensive blood donors, matched for age and sex. Serum IgA and IgM were the same in both groups. Raised levels of serum IgG were found in patients who had never been treated for hypertension, as well as in those who were treated with methyldopa or other hypotensive drugs.It is suggested that the raised levels of serum IgG may be an index of vascular damage induced by hypertension.     

孕期个性化营养干预对妊娠期糖尿病孕妇糖脂水平及妊娠结局的影响

目的:探讨孕期个性化营养干预对妊娠期糖尿病孕妇糖脂水平及妊娠结局的影响。方法:选择2016年8月-2017年10月期间于我院产检的妊娠期糖尿病孕妇160例,以随机数字表法分为研究组(n=80)和对照组(n=80)。对照组给予常规营养干预,研究组则予以孕期个性化营养干预。比较两组干预前后空腹血糖、餐后2h血糖、总胆固醇(TC)、三酰甘油(TG)、高密低脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平,观察孕妇及新生儿并发症发生情况。结果:干预后两组孕妇空腹血糖、餐后2 h血糖显著降低,且研究组低于对照组(P0.05)。干预后对照组孕妇TC、TG、LDL-C较干预前显著升高(P0.05),HDL-C差异无统计学意义(P0.05),研究组血脂水平与干预前比较差异无统计学意义(P0.05),与对照组比较,研究组孕妇TC、TG、LDL-C水平更低(P0.05)。研究组妊娠期高血压、胎膜早破发生率均明显低于对照组(P0.05),两组感染、产后出血发生率比较无统计学差异(P0.05)。与对照组比较,研究组新生儿窘迫、巨大儿、新生儿低血糖、早产儿的发生率降低(P0.05)。结论:孕期个性化营养干预可有效改善妊娠期糖尿病孕妇的糖脂水平,且能够有效降低并发症发生率,从而改善妊娠结局。     

Methyldopa and propranolol or practolol in moderate hypertension.

The effect of a low dose of methyldopa combined with (a) a non-selective and (b) a selective beta-adrenoceptor antagonist was studied in a double-blind crossover trial in 24 carefully selected patients with moderate hypertension (mean initial lying blood pressure 189/117 mm Hg). Each patient received methyldopa 750 mg/day, propranolol 240 mg/day, practolol 600 mg/day, methyldopa 750 mg/day combined with propranolol 240 mg/day, methyldopa 750 mg/day combined with practolol 600 mg/day, and placebo for four weeks each according to a random sequence. After four weeks of therapy the most effective treatment, methyldopa combined with propranolol, reduced lying and standing blood pressures by 36-5/21-4 mm Hg and 44-7/25 mm Hg respectively. Thic combination had similar effects to those of the combination of methyldopa with the cardioselective agent practolol except that it reduced lying diastolic pressure further. The combination was more effective than either treatment alone. No significant differences were found between the effects of propranolol, practolol, or methyldopa at the doses used.     

Report of the Canadian Hypertension Society Consensus Conference: 2. Nonpharmacologic management and prevention of hypertensive disorders in pregnancy

OBJECTIVE: To provide Canadian physicians with comprehensive, evidence-based guidelines for the nonpharmacologic management and prevention of gestational hypertension and pre-existing hypertension during pregnancy. OPTIONS: Lifestyle modifications, dietary or nutrient interventions, plasma volume expansion and use of prostaglandin precursors or inhibitors. OUTCOMES: In gestational hypertension, prevention of complications and death related to either its occurrence (primary or secondary prevention) or its severity (tertiary prevention). In pre-existing hypertension, prevention of superimposed gestational hypertension and intrauterine growth retardation. EVIDENCE: Articles retrieved from the pregnancy and childbirth module of the Cochrane Database of Systematic Reviews; pertinent articles published from 1966 to 1996, retrieved through a MEDLINE search; and review of original randomized trials from 1942 to 1996. If evidence was unavailable, consensus was reached by the members of the consensus panel set up by the Canadian Hypertension Society. VALUES: High priority was given to prevention of adverse maternal and neonatal outcomes in pregnancies with established hypertension and in those at high risk of gestational hypertension through the provision of effective nonpharmacologic management. BENEFITS, HARMS AND COSTS: Reduction in rate of long-term hospital admissions among women with gestational hypertension, with establishment of safe home-care blood pressure monitoring and appropriate rest. Targeting prophylactic interventions in selected high-risk groups may avoid ineffective use in the general population. Cost was not considered. RECOMMENDATION: Nonpharmacologic management should be considered for pregnant women with a systolic blood pressure of 140-150 mm Hg or a diastolic pressure of 90-99 mm Hg, or both, measured in a clinical setting. A short-term hospital stay may be required for diagnosis and for ruling out severe gestational hypertension (preeclampsia). In the latter case, the only effective treatment is delivery. Palliative management, dependent on blood pressure, gestational age and presence of associated maternal and fetal risk factors, includes close supervision, limitation of activities and some bed rest. A normal diet without salt restriction is advised. Promising preventive interventions that may reduce the incidence of gestational hypertension, especially with proteinuria, include calcium supplementation (2 g/d), fish oil supplementation and low-dose acetylsalicylic acid therapy, particularly in women at high risk for early-onset gestational hypertension. Pre-existing hypertension should be managed the same way as before pregnancy. However, additional concerns are the effects on fetal well-being and the worsening of hypertension during the second half of pregnancy. There is, as yet, no treatment that will prevent exacerbation of the condition. VALIDATION: The guidelines share the principles in consensus reports from the US and Australia on the nonpharmacologic management of hypertension in pregnancy.     

稳心颗粒治疗高血压性心脏病心律失常的疗效分析

目的:探讨稳心颗粒治疗高血压心脏病合并心律失常中的效果,为患者提供更好的治疗方案。方法:将110例高血压性心脏病合并心律失常患者随机分成对照组和治疗组,每组各55例。两组均进行常规的降压治疗,其中治疗组在常规治疗的基础上服用稳心颗粒,1袋/次,3次/d,6周为一个疗程。对比两组治疗效果。结果:治疗后,治疗组总有效率为89.1%(49/55)显著高于对照组的72.7%(40/55),差异具有统计学意义(P0.05);治疗组患者阵发性和永久性心房颤动占比分别5.5%(3/55)、0,低于对照组的12.7%(7/55),1.8%(1/55),其中阵发性心房颤动比较差异有统计学意义(P0.05);两组患者均未出现较明显的不良反应。结论:稳心颗粒治疗高血压心脏病合并心律失常中疗效确切,不良反应少。     

The dilemma of isolated systolic hypertension.

Isolated systolic hypertension, characterized by elevated systolic blood pressure (greater than 150 to 165 mm Hg), normal diastolic blood pressure (less than 90 to 95 mm Hg) and, often, atherosclerosis, is now recognized as an important risk factor for cardiovascular disease. When the systolic pressure is 200 mm Hg or greater, or when it is 180 mm Hg or greater and accompanied by target organ damage, therapeutic intervention may be of value in patients under the age of 80 years. Low doses of thiazide diuretics have been shown to be safe and effective in lowering the systolic pressure. If the blood pressure remains high, treatment with methyldopa may be added.