Familial dysautonomia (FD) patients frequently experience debilitating orthostatic hypotension. Since physical countermaneuvers can increase blood pressure (BP) in other groups of patients with orthostatic hypotension...Familial dysautonomia (FD) patients frequently experience debilitating orthostatic hypotension. Since physical countermaneuvers can increase blood pressure (BP) in other groups of patients with orthostatic hypotension, we evaluated the effectiveness of countermaneuvers in FD patients. In 17 FD patients (26.4 ± 12.4 years, eight female), we monitored heart rate (HR), blood pressure (BP), cardiac output (CO), total peripheral resistance (TPR) and calf volume while supine, during standing and during application of four countermaneuvers: bending forward, squatting, leg crossing, and abdominal compression using an inflatable belt. Countermaneuvers were initiated after standing up, when systolic BP had fallen by 40 mmHg or diastolic BP by 30 mmHg or presyncope had occurred. During active standing, blood pressure and TPR decreased, calf volume increased but CO remained stable. Mean BP increased significantly during bending forward (by 20.0 (17- 28.5) mmHg; P = 0.005) (median (25th - 75th quartile)), squatting (by 50.8 (33.5- 56) mmHg; P = 0.002), and abdominal compression (by 5.8 (- 1- 34.7) mmHg; P = 0.04) - but not during leg-crossing. Squatting and abdominal compression also induced a significant increase in CO (by 18.1 (- 1.3- 47.9) % during squatting (P = 0.02) and by 7.6 (0.4- 19.6) % during abdominal compression (P = 0.014)). HR did not change significantly during the countermaneuvers. TPR increased significantly only during squatting (by 37.2 (11.8- 48.2) % ; P = 0.01). However, orthopedic problems or ataxia prevented several patients from performing some of the countermaneuvers. Additionally, many patients required assistance with the maneuvers. Squatting, bending forward and abdominal compression can improve orthostatic BP in FD patients, which is achieved mainly by an increased cardiac output. Squatting has the greatest effect on orthostatic blood pressure in FD patients. Suitability and effectiveness of a specific countermaneuver depends on the orthopedic or neurological complications of each FD patient and must be individually tested before a therapeutic recommendation can be given.展开更多
脑损伤后发作性自主神经功能障碍伴肌张力增高（paroxysmal autonomic instability with dystonia,PAID）是严重脑损伤后出现的一种以间歇性谵妄、大汗、高热、高血压、心动过速、呼吸急促,同时伴肌张力异常、去皮质或去大脑强直、躁动...脑损伤后发作性自主神经功能障碍伴肌张力增高（paroxysmal autonomic instability with dystonia,PAID）是严重脑损伤后出现的一种以间歇性谵妄、大汗、高热、高血压、心动过速、呼吸急促,同时伴肌张力异常、去皮质或去大脑强直、躁动、瞳孔放大等为临床特征的综合征。展开更多
Context: Children with familial hypercholesterolemia have endothelial d ysfunct ion and increased carotid intimamedia thickness(IMT), which herald the premature atherosclerotic disease they develop later in life. Alth...Context: Children with familial hypercholesterolemia have endothelial d ysfunct ion and increased carotid intimamedia thickness(IMT), which herald the premature atherosclerotic disease they develop later in life. Although intervention thera py in the causal pathway of this disorder has been available for more than a dec ade, the long-term efficacy and safety of cholesterol-lowering medication have not been evaluated in children. Objective: To determine the 2-year efficacy an d safety of pravastatin therapy in children with familial hypercholesterolemia. Design: Randomized, double-blind, placebo-controlled trial that recruited chil dren between December 7, 1997, and October 4, 1999, and followed them up for 2 y ears. Setting and Participants: Two hundred fourteen children with familial hype rcholesterolemia, aged 8 to 18 years and recruited from an academic medical refe rral center in the Netherlands. Intervention: After initiation of a fat-restric ted diet and encouragement of regular physical activity, children were randomly assigned to receive treatment with pravastatin, 20 to 40 mg/d (n=106), or a plac ebo tablet (n=108). Main Outcome Measures: The primary efficacy outcome was the change from baseline in mean carotid IMT compared between the 2 groups over 2 ye ars; the principal safety outcomes were growth, maturation, and hormone level me asurements over 2 years as well as changes in muscle and liver enzyme levels. Re sults: Compared with baseline, carotid IMT showed a trend toward regression with pravastatin (mean <<SD>>, -0.010 <<0.048>> mm; P=.049), whereas a trend toward pro gression was observed in the placebo group (mean <<SD>>, +0.005 <<0.044>> mm; P=.28 ). The mean (SD) change in IMT compared between the 2 groups (0.014 <<0.046>> mm) was significant (P=.02). Also, pravastatin significantly reduced mean low-densi ty lipoprotein cholesterol levels compared with placebo (-24.1%vs +0.3%, res pectively; P< .001). No differences were observed for growth, muscle or liver en zymes, endocrine function parameters, Tanner staging scores, onset of menses, or testicular volume between the 2 groups. Conclusion: Two years of pravastatin th erapy induced a significant regression of carotid atherosclerosis in children wi th familial hypercholesterolemia, with no adverse effects on growth, sexual matu ration, hormone levels, or liver or muscle tissue.展开更多
文摘Familial dysautonomia (FD) patients frequently experience debilitating orthostatic hypotension. Since physical countermaneuvers can increase blood pressure (BP) in other groups of patients with orthostatic hypotension, we evaluated the effectiveness of countermaneuvers in FD patients. In 17 FD patients (26.4 ± 12.4 years, eight female), we monitored heart rate (HR), blood pressure (BP), cardiac output (CO), total peripheral resistance (TPR) and calf volume while supine, during standing and during application of four countermaneuvers: bending forward, squatting, leg crossing, and abdominal compression using an inflatable belt. Countermaneuvers were initiated after standing up, when systolic BP had fallen by 40 mmHg or diastolic BP by 30 mmHg or presyncope had occurred. During active standing, blood pressure and TPR decreased, calf volume increased but CO remained stable. Mean BP increased significantly during bending forward (by 20.0 (17- 28.5) mmHg; P = 0.005) (median (25th - 75th quartile)), squatting (by 50.8 (33.5- 56) mmHg; P = 0.002), and abdominal compression (by 5.8 (- 1- 34.7) mmHg; P = 0.04) - but not during leg-crossing. Squatting and abdominal compression also induced a significant increase in CO (by 18.1 (- 1.3- 47.9) % during squatting (P = 0.02) and by 7.6 (0.4- 19.6) % during abdominal compression (P = 0.014)). HR did not change significantly during the countermaneuvers. TPR increased significantly only during squatting (by 37.2 (11.8- 48.2) % ; P = 0.01). However, orthopedic problems or ataxia prevented several patients from performing some of the countermaneuvers. Additionally, many patients required assistance with the maneuvers. Squatting, bending forward and abdominal compression can improve orthostatic BP in FD patients, which is achieved mainly by an increased cardiac output. Squatting has the greatest effect on orthostatic blood pressure in FD patients. Suitability and effectiveness of a specific countermaneuver depends on the orthopedic or neurological complications of each FD patient and must be individually tested before a therapeutic recommendation can be given.
文摘脑损伤后发作性自主神经功能障碍伴肌张力增高（paroxysmal autonomic instability with dystonia,PAID）是严重脑损伤后出现的一种以间歇性谵妄、大汗、高热、高血压、心动过速、呼吸急促,同时伴肌张力异常、去皮质或去大脑强直、躁动、瞳孔放大等为临床特征的综合征。
文摘Context: Children with familial hypercholesterolemia have endothelial d ysfunct ion and increased carotid intimamedia thickness(IMT), which herald the premature atherosclerotic disease they develop later in life. Although intervention thera py in the causal pathway of this disorder has been available for more than a dec ade, the long-term efficacy and safety of cholesterol-lowering medication have not been evaluated in children. Objective: To determine the 2-year efficacy an d safety of pravastatin therapy in children with familial hypercholesterolemia. Design: Randomized, double-blind, placebo-controlled trial that recruited chil dren between December 7, 1997, and October 4, 1999, and followed them up for 2 y ears. Setting and Participants: Two hundred fourteen children with familial hype rcholesterolemia, aged 8 to 18 years and recruited from an academic medical refe rral center in the Netherlands. Intervention: After initiation of a fat-restric ted diet and encouragement of regular physical activity, children were randomly assigned to receive treatment with pravastatin, 20 to 40 mg/d (n=106), or a plac ebo tablet (n=108). Main Outcome Measures: The primary efficacy outcome was the change from baseline in mean carotid IMT compared between the 2 groups over 2 ye ars; the principal safety outcomes were growth, maturation, and hormone level me asurements over 2 years as well as changes in muscle and liver enzyme levels. Re sults: Compared with baseline, carotid IMT showed a trend toward regression with pravastatin (mean <<SD>>, -0.010 <<0.048>> mm; P=.049), whereas a trend toward pro gression was observed in the placebo group (mean <<SD>>, +0.005 <<0.044>> mm; P=.28 ). The mean (SD) change in IMT compared between the 2 groups (0.014 <<0.046>> mm) was significant (P=.02). Also, pravastatin significantly reduced mean low-densi ty lipoprotein cholesterol levels compared with placebo (-24.1%vs +0.3%, res pectively; P< .001). No differences were observed for growth, muscle or liver en zymes, endocrine function parameters, Tanner staging scores, onset of menses, or testicular volume between the 2 groups. Conclusion: Two years of pravastatin th erapy induced a significant regression of carotid atherosclerosis in children wi th familial hypercholesterolemia, with no adverse effects on growth, sexual matu ration, hormone levels, or liver or muscle tissue.
