Racial background is a determinant of average warfarin dose required to maintain the INR between 2.0 and 3.0

Warfarin is a commonly used prophylactic agent for the prevention of thromboembolic disease. We hypothesized that racial background influenced warfarin dosage, and tested this by recording the international normalized ratio (INR) in 867 patients aged 40-90 routinely passing through our Anticoagulation Service whose target INR was 2-3. Mean (95% confidence interval) dose was 4.1 (4.0-4.2) mg/d in 737 Caucasians, 5.5 (4.9-6.1) mg/d in 72 Asians, and 6.7 (5. 8-7.6) mg/d in 58 Afro-Caribbeans (P < 0.05) between each group). In a subgroup of 302 (41 Asians, 22 Afro-Caribbeans, 239 Caucasians), body mass index did not influence warfarin use. Despite small numbers, we conclude that racial background, but not body mass index, is a determinant of warfarin dosage. The reasons for this could be genetic, cultural (diet related), or both.     

口服华法令抗凝致出血的原因分析

目的:探讨口服华法令抗凝治疗期间患者出血的相关原因。方法:收集60例因口服华法令抗凝治疗期间合并出血的急诊患者的临床资料,分析在不同凝血酶原时间(PT-INR)值范围内导致出血的相关病因。结果:60例服用华法令合并出血的病例中,24例(40.0%)所测PT-INR在2.0~3.0的目标值内,并且9例患者INR<2.0;进一步检查发现这33例患者基本都合并有不同的易促使出血的疾病。结论:服用华法令抗凝治疗期间发生出血与否并不完全取决于PT-INR值,还决定于自身潜在的疾病等相关原因;临床应用华法令时应因人而异地调整剂量并决定其抗凝强度。     

长春市两个地区褐家鼠对杀鼠灵的抗药性实验研究

目的掌握长春市褐家鼠对第一代抗凝血灭鼠剂（杀鼠灵）的抗药性，从而指导长春市大面积的灭鼠用药。方法按照全国鼠类抗药性监测协作组制定的统一方法，进行无选择性摄毒试验。结果两个地区共56只试鼠，其中双阳区29只试验鼠，实验结束后有1只存活，其存活鼠摄药剂量为13．54mg／kg，为抗性鼠，抗性发生率为3．45％，没有形成抗性种群。结论褐家鼠对第一代抗凝血灭鼠剂有一定的耐药力，但根据判定标准的要求并没有产生抗药性种群，因此，在长春市可以继续使用第一代抗凝血灭鼠剂，同时应加强对第一代抗凝血灭鼠剂的敏感性和抗药性监测。     

Potentiation of anticoagulant response to Warfarin by Sulphinpyrazone: a double-blind study in patients with prosthetic heart valves

The effect of Sulphinpyrazone on the anticoagulant response to Warfarin was evaluated by a double-blind study in 11 patients with prosthetic heart valves. Six patients received Warfarin and Sulphinpyrazone and 5 Warfarin and placebo. Sulphinpyazone potentiated the anticoagulant effect of Warfarin. Patients receiving Sulphinpyrazone needed about half the amount of Warfarin as compared to the control group. There were four bleeding episodes in the Sulphinpyrazone group and one episode in the control group. It was difficult to regulate the dose of Warfarin in patients also receiving Sulphinpyrazone.     

Assembly mechanism is the key determinant of the dosage sensitivity of a phage structural protein

Altering the expression level of proteins that are subunits of complexes has been proposed to be particularly detrimental because the resulting stoichiometric imbalance among components would lead to misassembly of the complex. Here we show that assembly of the phage HK97 connector complex is severely inhibited by the overexpression of one of its component proteins, gp6. However, this effect is a result of the unusual mechanism by which the oligomerization and assembly of gp6 are controlled. Alteration of this mechanism by single amino acid substitutions leads to a reversal of the response to gp6 overexpression. Surprisingly, the binding partner of gp6 within the phage particle is expressed at a 500-fold higher concentration despite their identical stoichiometry within the complex. Our data emphasize that a generalized prediction of the effects of changes in the expression level of protein complex subunits is very difficult because these effects are dependent upon assembly mechanism.     

胺碘酮与华法林合用对老年房颤病人INR的影响

目的：探讨胺碘酮对使用华法林抗凝治疗的房颤患者凝血酶原时间国际标准化比值（INR）的影响.方法：选择48例华法林抗凝治疗的持续性房颤患者,随机分为：华法林治疗组（24例）,维持原剂量华法林抗凝治疗;联合治疗组（24例）,在常规治疗基础上加用盐酸胺碘酮（可达龙）200mg,1日3次口服,治疗1周,测定并观察两组患者治疗前后INR的变化.结果：联合治疗组INR较华法林治疗组明显增高（P〈0.05）.结论：胺碘酮会增加华法林抗凝作用,治疗过程应注意监测INR,以调整华法林用量.     

瘦组织是甲状腺疾病治疗中左旋甲状腺素用量的主要决定因素

左旋甲状腺素(L-T4)是甲状腺疾病的常用药物，多用于纠正各种原因引起的甲状腺激素缺乏症，以及甲状腺癌或甲状腺结节患者抑制促甲状腺素(TSH)。临床观察发现，服用L-T4的患者，在药物剂量上存在着个体差异，除了患者当时的甲状腺功能和其他有关的生理病理状态(如妊娠等)外，还与患者的年龄、性别、体型等有关，其中体重，特别是瘦组织(lean body mass)含量是老年人甲状腺激素每日需要量的主要决定因素。     

540例持续性心房颤动患者华法林抗凝治疗安全性的临床观察

为评价华法林用于持续性心房颤动 (简称房颤 )患者抗凝治疗的安全性 ,对 5 4 0例持续性房颤患者进行华法林抗凝治疗 ,观察治疗过程中的出血及其它不良反应。结果 :华法林用量为 2 .5 4± 0 .7(1～ 6 )mg/d ,治疗维持国际标准化率 (INR)在 2～ 3范围时 ,轻度出血率为 3.15 % ,经相关处理并调低INR值 ,所有出血均停止 ;无一例因严重出血而终止抗凝治疗 ;未见其它不良反应。 75岁以上房颤者出血发生率增加。结论 :持续性房颤患者应用华法林抗凝治疗时 ,INR维持在 2～ 3范围可能是安全的 ;轻度出血患者经调低INR值 ,出血可以停止 ,不影响继续抗凝治疗。     

Lean body mass is a major determinant of levothyroxine dosage in the treatment of thyroid diseases

Total body weight is usually employed to calculate the amount of l-T(4) to be administered in patients with thyroid diseases. The aim of this study was to evaluate the effect of body composition on l-T(4) requirements. Body composition was assessed by dual energy x-ray absorptiometry in 75 patients on TSH-suppressive l-T(4) therapy after conventional thyroid ablation for differentiated cancer. The mean daily dose of l-T(4) was lower in normal-weight (127.5 +/- 21.3 mug/d) vs. overweight (139.4 +/- 24.5) and obese (151.3 +/- 29.1) subjects. There was a much stronger association between the l-T(4) dosage and lean body mass (P < 0.001, r = 0.667) compared with fat mass (P = 0.023, r = 0.26). Measurement of regional tissue composition showed peripheral lean mass as the best correlate with the dose of l-T(4) (r = 0.679, P < 0.001) whereas no correlation was observed with peripheral fat mass. In conclusion, individual l-T(4) requirements are dependent on lean body mass. Age- and gender-related differences in l-T(4) needs reflect different proportions of lean mass over the total body weight. An estimate of lean mass may be helpful to shorten the time required to attain a stable dose of l-T(4), particularly in subjects with high body mass index values that may be due either to increased muscular mass or to obesity.     

Transition from Acenocoumarol to Warfarin in a 12‐year‐old Child

The types of coumadin anticoagulants registered and available for use differ between countries. Most frequently used coumadin anticoagulants are warfarin and acenocoumarol. Under several specific conditions, transition from one coumarin to another is required. Because of different pharmacokinetic and pharmacodynamic characteristics, the transition from one type of coumarol to another type can be challenging. There are no studies that address this issue in children. We present the case report of transition treatment between acenocoumarol and warfarin in a 12‐year‐old child with prosthetic mitral valve.     

北京市房山区老年非瓣膜性房颤的华法林抗凝治疗研究

目的：研究适宜剂量的华法林对北京市房山区65岁以上老年持久性非瓣膜性房颤（NVAF）患者的疗效。方法：对纳入研究的870例持久性NVAF患者抗凝治疗资料进行回顾性分析。患者被分为阿司匹林组（471例）和调整剂量华法林（维持INR在2．0～3．0）组（369例）。两组在年龄、性别、伴随病等方面无显著差异。比较两组主要、次要终点事件。结果：入选病例共937例,有效病例870例,失访67例（7．1％）。随访时间（19．2±2．1）个月。华法林组主要终点事件（死亡和缺血性脑卒中）较阿司匹林组降低62％（1．06％：6．52％,P=0．04）。华法林组的缺血性脑卒中较阿司匹林组下降68％（0．42％：4．76％,P=0．04）;华法林组总死亡率低于阿司匹林组（0．42％：3．00％,P=0．02）。包括主要和次要终点的联合终点事件华法林组低于阿司匹林组（2．97％：13．03％,P=0．04）。华法林组出血率较阿司匹林组显著减少（1．69％：12．02％,P=0．04）。结论：对于老年持久性非瓣膜性房颤患者,给予华法林维持INR在2．0～3．0的剂量,可以较阿司匹林更大程度地降低并发症和死亡率,而且是安全的。     

Racial differences in blood pressure control: potential explanatory factors

Purpose

Poor blood pressure control remains a common problem that contributes to significant cardiovascular morbidity and mortality, particularly among African Americans. We explored antihypertensive medication adherence and other factors that may explain racial differences in blood pressure control.

Methods

Baseline data were obtained from the Veteran’s Study to Improve The Control of Hypertension, a randomized controlled trial designed to improve blood pressure control. Clinical, demographic, and psychosocial factors relating to blood pressure control were examined.

Results

A total of 569 patients who were African American (41%) or white (59%) were enrolled in the study. African Americans were more likely to have inadequate baseline blood pressure control than whites (63% vs 50%; odds ratio = 1.70; 95% confidence interval [CI] 1.20-2.41). Among 20 factors related to blood pressure control, African Americans also had a higher odds ratio of being nonadherent to their medication, being more functionally illiterate, and having a family member with hypertension compared with whites. Compared with whites, African Americans also were more likely to perceive high blood pressure as serious and to experience the side effect of increased urination compared with whites. Adjusting for these differences reduced the odds ratio of African Americans having adequate blood pressure control to 1.59 (95% confidence interval 1.09-2.29).

Conclusions

In this sample of hypertensive patients who have good access to health care and medication benefits, African Americans continued to have lower levels of blood pressure control despite considering more than 20 factors related to blood pressure control. Interventions designed to improve medication adherence need to take race into account. Patients’ self-reports of failure to take medications provide an opportunity for clinicians to explore reasons for medication nonadherence, thereby improving adherence and potentially blood pressure control.     

非瓣膜病房颤的华法林抗凝治疗研究

目的：应用华法林对非瓣膜病性心房颤动患者进行抗凝治疗,观察其抗栓疗效和安全性。方法：服用华法林．从3．0mg。1次／d开始．根据血浆凝血酶原时间国际标准化比率（INR）调整华法林剂量．低抗凝强度组患者（46例）INR为1．5～2．1．标准抗凝强度组患者（66例）INR为2．2～3．0．两组均持续服药,随访1～4年．观察有无血栓栓塞事件及出血并发症。结果：低抗凝强度组中有1例发生脑栓塞,当时INR为1．5．栓塞年发生率为2．2％;标准抗凝强度组无栓塞并发症．两组比较差异无显著性（P〉0．05）。服用华法林期间．低抗凝强度组1例肉眼血尿,出血年发生率为2．2％;标准抗凝强度组发生皮肤黏膜出血4例．牙龈出血3例,球结膜出血1例．出血年发生率为12％。当时的INR除3例为〉3．其余均在2．6～3．0之间,未发生严重大出血．低抗凝强度组出血发生率显著低于标准抗凝血组（P〈0．05）。结论：房颤患者华法林抗凝目标INR值在1．5-3．0安全有效。     

Pre-treatment IGF-I level is the major determinant of GH dosage in adult GH deficiency

OBJECTIVE: Severe GH deficiency in adults is a definite clinical entity, the effects of which can be reversed by administration of subcutaneous recombinant GH. The ideal dosing regimen and determinants of the maintenance dose have, however, yet to be elucidated. PATIENTS: In an open study of GH replacement we treated 65 GH-deficient adults of mixed adult- and childhood-onset, of mean age 35.5 (range 17-72) years, and comprising 38 females and 27 males, using an individualized low-dose titration regimen aimed at normalization of the serum IGF-I and induction of clinical improvement. RESULTS: Before initiation of GH therapy, median IGF-I SD was significantly lower in female than male patients (- 3.3 vs. - 1.9, P = 0.007) and in childhood-onset compared with adult-onset patients (- 3.9 vs. - 2.0, P < 0.001). Once maintenance dosage had been achieved, the median GH requirement was significantly greater in female than male patients (1.6 vs. 0.8 IU/day, P = 0.013) and childhood-onset compared with adult-onset patients (1.6 vs. 0.8 IU/day, P = 0.019). The median maintenance GH dose for the cohort overall was 1.2 (range 0.4-2.4) IU/day. By univariate analysis a significant negative correlation was observed between the maintenance GH dose and baseline IGF-I SD (r = - 0.63, P < 0.001). No significant correlation was demonstrated between maintenance GH dose and either age or weight. Multiple linear regression analysis using age, gender, weight, time of onset of GH deficiency, peak GH to the insulin tolerance test (ITT) and baseline IGF-I SD as independent variables demonstrated baseline IGF-I SD to account for 51% of the variation in GH dose required to normalize the IGF-I SD (P < 0.001). Those patients with the lower IGF-I SD at initiation of GH therapy required the greater GH dose. None of the other variables studied significantly influenced the maintenance dose. CONCLUSION: We have demonstrated that the GH dose required in an individual is dependent on the serum IGF-I SD before commencement of replacement. In contrast, the severity of GH deficiency as judged by the peak GH response to an ITT was unrelated to the maintenance GH requirement. The effect of age, gender and age at onset of GH deficiency on the final GH dose are accounted for by the lower pretreatment IGF-I SD in young, female and childhood-onset patients relative to older, male and adult-onset patients, respectively.     

Racial susceptibility for QT prolongation in acute drug overdoses

Background and Purpose

QT prolongation independently predicts adverse cardiovascular events in suspected poisoning. We aimed to evaluate the association between race and drug-induced QT prolongation for patients with acute overdose.

Methods

This was a cross-sectional observational study at two urban teaching hospitals. Consecutive adult ED patients with acute drug overdose were prospectively enrolled over a two year period. The primary outcome, long-QT, was defined using standard criteria: QTc > 470 ms in females and > 460 ms in males. The association between race and drug-induced QT prolongation was tested, considering several confounding variables.

Results

In 472 patients analyzed (46% female, mean age 42.3), QT prolongation occurred in 12.7%. Blacks had two-fold increased odds of drug-induced QT prolongation (OR 2.01, CI 1.03–3.91) and Hispanics had 48% decreased odds of drug-induced QT prolongation (OR 0.52, CI 0.29–0.94).

Conclusions

We found significant racial susceptibility to drug-induced QT prolongation in this large urban study of acute overdoses.     

房颤抗凝治疗华法令合适剂量的临床对照分析

目的评价华法林用于心房颤动病人抗凝治疗的合适剂量和安全性。方法95例房颤病人随机分为2组,用不同剂量华法林治疗:治疗组45例,INR2.0~2.5;对照组50例,INR:1.5~2.0。结果治疗组与对照组比较,脑栓塞的发生率无显著性差异,脑出血、大出血、死亡事件的发生率也无显著性差异。结论INR保持在1.5~2.0之间的低剂量华法林在房颤病人中的使用是安全有效的。     

Improving Warfarin Management Within the Medical Home: A Health-System Approach

Background

Anticoagulation clinics have been considered the optimal strategy for warfarin management with demonstrated improved patient outcomes through increased time in therapeutic international normalized ratio (INR) range, decreased critical INR values, and decreased anticoagulation-related adverse events. However, not all health systems are able to support a specialized anticoagulation clinic or may see patient volume exceed available anticoagulation clinic resources. The purpose of this study was to utilize an anticoagulation clinic model to standardize warfarin management in a primary care clinic setting.

Ulcerative colitis in a multiracial Asian country: Racial difference and clinical presentation among Malaysian patients

AIM: To determine the prevalence of ulcerative colitis (UC) in Malaysian patients and to establish the spectrum of the disease seen in Malaysian patients. METHODS: Data were obtained retrospectively from a review of the medical records of in- and out-patients with a diagnosis of UC at the University Hospital, Kuala Lumpur between 1985 and 1998. RESULTS: There were 45 confirmed cases of UC, of which 3 were foreigners, who were excluded from analysis. Thirty new cases of UC were diagnosed during the study period. Their mean age at presentation was 33.0±10.0 years. The highest prevalence of UC was 17.9/100 000 hospital admissions in the Indians, followed by 11.2/100 000 hospital admissions in the Chinese. The lowest prevalence was 3.7/100 000 hospital admissions in the Malays. The prevalence of UC was significantly higher in the Indians and the Chinese when compared with the Malays with an OR of 4.89 (CI=2.02-12.24; X~2=15.45, P<0.001) and 3.06 (CI=1.24-7.78; X~2=6.30; P=0.012) respectively. The extent of colonic disease was similar in the Malay and Indian patients. In contrast, distal or left-sided colitis predominated in the Chinese with an OR of 8.17 (95%CI=1.31-64.87; X~2=5.53, P=0.02). Extraintestinal manifestations were uncommon (11.9%). CONCLUSION: UC is an uncommon disease in Malaysia, but racial differences exist. The Indians had the highest prevalence of UC with the Chinese demonstrating the least extensive disease.