Warfarin and Statins are Associated with Hematoma Volume in Primary Infratentorial Intracerebral Hemorrhage

Background and purpose

Despite extensive studies of supratentorial intracerebral hemorrhage (ICH), limited data are available on determinants of hematoma volume in infratentorial ICH. We therefore aimed to identify predictors of infratentorial ICH volume and to evaluate whether location specificity exists when comparing cerebellar to brainstem ICH.

Methods

We undertook a retrospective analysis of 139 consecutive infratentorial ICH cases (95 cerebellar and 44 brainstem ICH) prospectively enrolled in a single-center study of ICH. ICH volume was measured on the CT scan obtained upon presentation to the Emergency Department using an established computer-assisted method. We used linear regression to identify determinants of log-transformed ICH volume and logistic regression to evaluate their role in surgical evacuation.

Results

Median ICH volumes for all infratentorial, cerebellar, and brainstem ICH were nine [interquartile range (IQR), 3–23], ten (IQR, 3–25), and eight (IQR, 3–19) milliliters, respectively. Thirty-six patients were on warfarin treatment, 31 underwent surgical evacuation, and 65 died within 90 days. Warfarin was associated with an increase in ICH volume of 86 % [β = 0.86, standard error (SE) = 0.29, p = 0.003] and statin treatment with a decrease of 69 % (β = ?69, SE = 0.26, p = 0.008). Among cerebellar ICH subjects, those on warfarin were five times more likely to undergo surgical evacuation (OR = 4.80, 95 % confidence interval 1.63–14.16, p = 0.005).

Conclusions

Warfarin exposure increases ICH volume in infratentorial ICH. Further studies will be necessary to confirm the inverse relation observed between statins and ICH volume.     

Abnormal prothrombin crossed-immunoelectrophoresis in patients with lupus inhibitors

Prothrombin deficiency has been known to occur in association with lupus inhibitors for over 25 years. We studied 21 patients with lupus inhibitors and found that four of five with prothrombin deficiency and ten of 16 with quantitatively normal prothrombin had abnormal prothrombin crossed-immunoelectrophoresis (CIEP) characterized by material moving slower in the first dimension of electrophoresis than normal prothrombin. In two patients with prothrombin deficiency, all prothrombin measured by quantitative assay and all slow-moving material on CIEP were removed by treatment with Staphylococcal protein A (SPA). These patients had free antibody, which bound to normal plasma prothrombin, forming larger amounts of slow-moving material on CIEP. A third patient with prothrombin deficiency had only partial removal of prothrombin after SPA treatment. Two patients with quantitatively normal prothrombin had all slow-moving material on CIEP and about one fourth of the prothrombin by quantitative assay removed by SPA treatment. There was no correlation among the strength of the inhibitor, the presence of a "cofactor effect," and the prothrombin abnormality. These data suggest that heterogeneous antiprothrombin antibodies, with or without prothrombin deficiency, are present in the majority of patients with lupus inhibitors.     

八肽胆囊收缩素对肿瘤坏死因子α诱导的大鼠滑膜细胞株RSC-364核因子κB活性变化的影响及其受体机制

目的:观察硫酸化八肽胆囊收缩素(cholecystokinin octapeptide,CCK-8)对肿瘤坏死因子α诱导大鼠滑膜细胞株RSC-364核因子κB的影响,以及CCK-A/B受体是否参与这一过程。方法:实验于2003-02/2004-02在河北医科大学法医学教研室分子生物学实验室完成。取大鼠滑膜细胞株RSC-364经肿瘤坏死因子α(10 μg/L)、sCCK-8(10-8,10-7,10-6 mol/L)、CCK受体拮抗剂丙谷胺及溶剂单独或联合应用孵育:①孵育3h,用反转录-聚合酶链反应技术检测细胞CCK-A受体及CCK-B受体mRNA的表达。②孵育1h,用电泳迁移率检测核因子κB相对活性。③孵育30 min,用Western blot检测胞浆IκB蛋白表达的相对水平。结果:①细胞CCK-A受体及CCK-B受体mRNA的表达:RSC-364细胞固有表达CCK-A/B受体,肿瘤坏死因子α(10 μg/L)可使CCK-A受体和CCK-B受体mRNA的表达分别上调148%和173%(P<0.01)。肿瘤坏死因子α和CCK-8(10-8～10-6 mol/L)联合孵育细胞,CCK-A受体和CCK-B受体mRNA表达与肿瘤坏死因子α组相比分别增高47%,56%,30%和57%,13%,24%(P<0.05,0.01)。②核因子κB相对活性:肿瘤坏死因子α组明显高于对照组(294.45±36.48,0,P<0.01);肿瘤坏死因子α CCK-810-8,10-7,10-6 mol/L组高于肿瘤坏死因子α组(470.69±56.76,489.37±64.95,558.90±74.15,P<0.05,0.01);CCK-8的作用可被丙谷胺减弱(400.79±39.06)。③IκB蛋白表达的相对水平:肿瘤坏死因子α组明显低于对照组(139.43±30.76,220.79±34.58,P<0.01),肿瘤坏死因子α CCK-810-8,10-7,10-6 mol/L组低于肿瘤坏死因子α组(95.26±8.54,84.15±8.77,63.28±16.13,P<0.05),并可被丙谷胺所抑制(137.22±20.33,P<0.01)。结论:CCK-8对肿瘤坏死因子α诱导的RSC-364核因子κB活性具有正向调节作用,并能降低IκBα蛋白水平,提示CCK-8在类风湿性关节炎发病过程中可能具有调控作用,此作用可能通过滑膜细胞上的CCK受体实现。     

Prognostic impact of cytogenetic abnormalities in patients with de novo acute nonlymphocytic leukemia

Detailed cytogenetic analyses were performed on specimens from 198 patients with de novo acute nonlymphocytic leukemia (ANLL), including high-resolution banding studies in 79 patients. One hundred ninety-two patients received induction therapy with daunorubicin and cytosine arabinoside (Ara-C) with an overall complete response rate (CR) of 63%. Responding patients received repetitive cycles of Ara-C-based intensification therapy. Clonal abnormalities were detected in 69% of the patients with specimens adequate for cytogenetic analysis. Certain cytogenetic changes were closely associated with French-American- British (FAB) morphology, age, and outcome: t(8;21) (closely associated with FAB M2), t(15;17) (associated with FAB M3), and abn 16q22 (associated with FAB M4EOS) tended to occur in younger patients and were associated with favorable outcomes in terms of both CR rate and long-term disease-free survival. In contrast, 19% of patients who had - 5/5q- and or -7/7q- and seven patients with trisomy 8 were older, had a poor prognosis, and usually failed to achieve remission (CR) because of chemotherapy-resistant leukemia. The adverse effect on CR rate and duration in this group of patients was independent of age, and there was no association with particular morphologic subtypes. These data suggest that cytogenetic findings should influence future therapeutic choices. In particular, patients with abnormalities associated with poor responses may be considered for investigational approaches and may also provide insights into mechanisms of drug resistance.     

Emergency department utilization by adolescents in the United States

BACKGROUND: Adolescents in the United States have been shown to underutilize primary care services and therefore may rely heavily on emergency service. Although several small studies have explored local emergency services for youth, there are no published reports of adolescent utilization of emergency services on a national scale. Furthermore, emergency services data have not been aggregated according to the age subgroups used by the current guidelines for adolescent care. OBJECTIVE: To explore the utilization of emergency departments in the United States by early (11 to 14 years), middle (15 to 17 years), and late (18 to 21 years) adolescent subgroups. DESIGN: Secondary analysis of the emergency department component of the 1994 National Hospital Ambulatory Medical Care Survey. SETTING: Nationally representative sample of 418 emergency departments in the United States. PATIENTS: Approximately 26,547 visits by patients of all ages, representing 93.4 million total visits in 1994 and 14.8 million adolescent visits. OUTCOME MEASURES: Number of visits, health insurance, reasons for visits, urgency of visits, resulting diagnoses, and hospitalization rates. RESULTS: Adolescents accounted for 15.4% of the population and 15.8% of emergency department visits in 1994. Late adolescents were overrepresented in emergency department visits relative to their population proportion (6.8% of visits, 5.3% of population), whereas early adolescents were underrepresented (4.6% of visits, 5.9% of population). Lack of health insurance was more common among 11- to 21-year-olds (26.2%) than either children (13.6%) or adults (22.7%). By ages 18 to 21 years, 40.5% of male visits and 27.6% of female visits were uninsured. Injury-related visits were more common among adolescents (28.6%) than either children (23.1%) or adults (18.2%). Injury was the leading reason for visits among all adolescent age-sex subgroups (36.6% to 42.0% of male visits and 14.1% to 27.2% of female visits) except females aged 18 to 21 years for whom digestive reasons ranked first (18.8%). Injury was the leading diagnosis for all adolescent age-sex subgroups, with peaks at early adolescence of 61.6% for males and 45.8% for females. Across all adolescent age-sex subgroups, 3.1% to 5.3% of visits resulted in hospitalization, and 41.0% to 52.5% of visits were urgent. These rates did not differ from those of children but were lower than those of adults. CONCLUSIONS: Utilization of emergency departments increases and health insurance decreases during adolescence, suggesting that adolescents with inadequate health insurance may rely heavily on emergency departments for their health care needs. Most adolescent visits to emergency departments are not urgent and might be better treated through nonemergency, primary care sites.     

Neonatal respiratory mechanics and development of bronchial hyperresponsiveness in preterm infants

BACKGROUND: In preterm ventilated infants, irreversible damage to the airway mucosa in the neonatal period might be related to the development of bronchial hyperresponsiveness (BHR) in subsequent years. AIMS: To evaluate whether neonatal indicators of long-term respiratory morbidity, respiratory system compliance (Crs) and resistance (Rrs), were causally related to bronchial responsiveness at the age of 2 and whether these relationships were affected by other factors. STUDY DESIGN: Mean neonatal Crs and Rrs of the first 3 days of life were assessed using the single breath occlusion technique. Bronchial challenge tests were performed at 2 years of age. When wheezing occurred during chest auscultation or oxygen saturation decreased below 90%, the provocative concentration of methacholine was recorded. SUBJECTS: Forty-five preterm infants of <37 weeks gestation, being mechanically ventilated within 24 h after birth. RESULTS: Decreased neonatal Crs was related to BHR (beta per ml/kPa, 0.061; 95% confidence interval, 0.019 to 0.103; p=0.006). Correction was required for radiological gradation of respiratory distress syndrome, the maximal peak inspiratory pressure required during mechanical ventilation and postnatal corticosteroid therapy. Neonatal Rrs, gestational age and birth weight were not related to subsequent BHR development. CONCLUSION: In ventilated preterm infants, decreased neonatal Crs was related to the development of BHR at the age of 2.