Combined oral lysine acetylsalicylate and metoclopramide in the acute treatment of migraine: a multicentre double-blind placebo-controlled study

This multicentre, double-blind, randomized, placebo-controlled, parallel study was designed to evaluate the efficacy of combined oral lysine acetylsalicylate and metoclopramide (LAS-MCP) in the acute treatment of migraine attacks. A total of 266 patients, 18–65 years old, with two to six attacks of migraine with or without aura (IHS criteria) per month were included. The patients had to treat two migraine attacks with LAS-MCP (1620 mg lysine acetylsalicylate-the equivalent of 900 mg aspirin- combined with 10 mg metoclopramide) or placebo. The main outcome measure was headache relief (reduction in headache severity from grade 3 or 2-severe or moderate-to grade 1 or 0-mild or none) 2 h after treatment. LAS-MCP was superior to placebo for headache relief (56% vs 28%) and for the following secondary outcome measures: complete headache relief (18% vs 7%; p < 0.001), nausea (28% vs 44%; p < 0.001), vomiting (3% vs 11%; p = 0.001), use of rescue medication (47% vs 68%; p < 0.001), global efficacy judged as good or excellent (32% vs 14%; p < 0.001). The tolerability was considered as good in 94% of treated attacks in both groups. Combined oral lysine acetylsalicylate and metoclopramide is an effective and well-tolerated acute treatment of migraine attacks.     

Effective removal of copper by plasma exchange in fulminant Wilson's disease

BACKGROUND: Patients who present with fulminant hepatic failure due to Wilson's disease may develop hemolytic anemia and renal insufficiency. In this entity, acute hepatocellular necrosis triggers the release of copper ions into the circulation, which leads to toxic effects on red cell metabolic pathways and hemolysis. STUDY DESIGN AND METHODS: The utility of therapeutic plasma exchange to rapidly remove copper and reduce toxic serum copper levels was studied in two patients with fulminant Wilson's disease. RESULTS: Intensive plasma exchange using fresh-frozen plasma replacement removed substantial amounts of copper from the hypercupremic patients, resulting in a rapid reduction in serum copper levels and decreased hemolysis. The net copper removal was proportional to the serum level, ranging from 7,000 to 11,800 micrograms per procedure in one patient and from 3,700 to 6,800 micrograms in the other. CONCLUSION: Plasma exchange allows a rapid reduction in elevated serum copper levels in patients with fulminant Wilson's disease. This leads to an amelioration of hemolytic anemia and provides clinical stabilization until liver transplantation can be performed.     

The effect of sterilization on transforming growth factor beta isolated from demineralized human bone

Growth factors have been identified as the primary cause of osteoinduction in bone healing. Transforming growth factor beta (TGF- beta) has been shown to promote bone formation and is present in bone in high quantities. The aims of the present study were to isolate TGF- beta from human bone, demonstrate its biologic activity, and analyze the effects of conventional sterilization techniques on activity. Bone, obtained from femoral heads of five patients (mean age, 70 years) was ground, demineralized, and freeze-dried, and samples from each patient were divided into three groups: no treatment, sterilization with 1.60 to 1.94 Mrad of 60Co irradiation, and sterilization with ethylene oxide (ETO). Carrier-free recombinant TGF-beta control was also treated and was totally inactivated by ETO but not by irradiation (p < 0.01). TGF- beta activity in demineralized bone was not significantly diminished (p > 0.1) by either sterilization procedure, and substantial amounts of active TGF-beta were recovered in all bone samples: 1.04 +/− 0.77 ng per mg of protein in irradiated samples, 0.67 +/− 0.26 ng per mg in ETO- treated samples, and 1.04 +/− 0.33 in untreated samples, respectively (mean +/− SD). Although a recent report demonstrated that the osteoinductive activity of bone morphogenetic protein in bone powder is diminished considerably by ETO and by 2.5 Mrad of irradiation sterilization of bone powder, these data demonstrate that TGF-beta activity, with its osteoinductive properties, was not destroyed in more coarsely ground, demineralized bone by ETO or by lower doses of irradiation. These findings support the use of human bone allografts in clinical instances involving impaired bone formation.     

碱性成纤维细胞生长因子对大鼠脑血肿周围组织和海马bax及bcl-2基因表达的调节

目的:观察碱性成纤维细胞生长因子对大鼠脑出血后出血灶周围脑组织和出血侧海马bax、bcl-2基因表达的影响,探讨神经营养因子对神经细胞调亡的调控。方法:实验于2006-01/10在广西医科大学医学科学实验中心完成。①取成年清洁级Wistar大鼠72只,雌雄各半,体质量250g左右。②采用脑内囊注射胶原酶建立大鼠脑出血模型,动物于苏醒后按Bederson法进行神经病学评分,评分>3分后入选本实验,入选72只大鼠随机抽签法分为3组,每组24只。碱性成纤维细胞生长因子组按8μg/kg剂量肌肉注射,1次/d;生理盐水组肌肉注射等剂量的生理盐水,1次/d;模型组不作任何干预。③每组分别于干预后1,3,7d随机抽取8只大鼠,麻醉状态下取出血灶周围脑组织和出血侧海马,采用半定量反转录-聚合酶链反应检测调亡调控基因bax mRNA,bcl-2mRNA的表达。结果:在建立脑出血模型中共5只大鼠死亡,随后对死亡动物进行解剖,发现脑内血肿量过大,致脑疝形成而导致死亡,后随机补充动物。72只大鼠进入结果分析。①血肿周围脑组织bax mRNA表达:干预后3d,7d,碱性成纤维细胞生长因子组血肿周围脑组织bax mRNA表达比生理盐水组明显减少(3d:0.54±0.19,0.76±0.23,P<0.05;7d:0.45±0.19,0.71±0.16,P<0.01)。②血肿周围脑组织bcl-2mRNA表达:干预后3d,7d,碱性成纤维细胞生长因子组的血肿周围脑组织bcl-2mRNA表达比生理盐水组明显增高(3d:0.68±0.25,0.39±0.19,P<0.05;7d:0.80±0.21,0.48±0.18,P<0.01)。③出血侧海马bax mRNA表达:干预后3d和7d,碱性成纤维细胞生长因子组的出血侧海马bax mRNA表达比生理盐水组均明显减少(3d:0.54±0.18,0.70±0.11;7d:0.43±0.24,0.69±0.18,P均<0.05)。④出血侧海马bcl-2mRNA表达:干预后3d和7d,碱性成纤维细胞生长因子组的出血侧海马bcl-2mRNA表达比生理盐水组均明显增多(3d:0.66±0.11,0.50±0.15;7d:0.72±0.12,0.52±0.22,P均<0.05)。结论:碱性成纤维细胞生长因子能调节凋亡相关基因,提高大鼠脑出血后大脑脑组织和海马bcl-2mRNA的表达,降低bax mRNA的表达。     

Translocation breakpoints are clustered on both chromosome 8 and chromosome 21 in the t(8;21) of acute myeloid leukemia

The t(8;21)(q22;q22) is consistently associated with acute myeloid leukemia (AML) M2. Recent data have suggested that breakpoints on chromosome 21 are clustered within a single intron of a novel gene, AML1, just downstream of a region of homology to the runt gene of D melanogaster. In this report, we confirm rearrangement at the same location in at least 12 of 18 patients with t(8;21). Furthermore, we have isolated recombinant clones spanning the breakpoint regions on both the der(8) and the der(21) from one patient. By using a chromosome 8 probe derived from these clones, we show that t(8;21) breakpoints are also clustered on chromosome 8.     

Open-access transvaginal sonography in women of reproductive age with abnormal vaginal bleeding: a descriptive study in general practice

Background

Diagnostic ultrasonography is used by GPs in approximately 10% of patients of reproductive age with abnormal vaginal bleeding. Transvaginal sonography is recommended as a first-line diagnostic instrument for assessing uterine pathology.

Aim

To assess if findings resulting from openaccess sonography were in agreement with the GPs’ working hypotheses and if these findings contributed to GPs’ management.

Design and setting

Prospective observational cohort study of GPs working in the health district of the Academic Medical Center, Amsterdam and their patients consulting with abnormal vaginal bleeding.

Method

Data on patients’ history, GPs’ primary working hypotheses, and intended management were recorded. After sonography, GPs recorded their actual management.

Results

A total of 122 patients were included by 18 GPs from June 2003 to December 2004. Data from 89 patients were available for analysis. The GPs’ working hypotheses implied ‘no structural pathology’ in 65/89 patients, and ‘fibroids’ in 24/89 patients. Sonographic findings were confirmed in 50/65 patients where ‘no structural pathology’, and in 14/24 of those where ‘fibroids’ were expected. Initially, GPs had intended to refer nine patients to a gynaecologist. Actual management after sonographic assessment was watchful waiting or drug therapy in 57/89 patients. Eighty-nine per cent of these patients had normal sonographic findings. The actual referral rate rose to 27/89 patients. In 17 referred patients, sonographic findings were suggestive of intracavitary abnormalities.

Conclusion

Open-access sonography contributed to more accurate diagnoses and improved GPs’ management of women with abnormal vaginal bleeding.     

Nationwide Implementation of Hello World: A Dutch Email-Based Health Promotion Program for Pregnant Women

Background

In November 2006, an email-based health promotion program for pregnant women was implemented nationally in the Netherlands. The program consisted of emails containing quizzes with pregnancy-related questions tailored to the number of weeks of pregnancy. Emails were sent out once every 4 weeks, up to a maximum of nine emails.

Objectives

The aims of the study were (1) to assess the recruitment of participants and their representativeness of the Dutch population and (2) to study differences in recruitment, program use, and program appreciation among women with different levels of education.

Methods

Data from 13,946 pregnant women who enrolled during the first year of the program were included. Upon registration, participants were asked how they found out about the program and subsequently received an email questionnaire to assess demographic, lifestyle, and Internet characteristics. Program use was tracked, and participants were classified into five user groups (inactive to very active). Program appreciation (low, intermediate, and high) was assessed twice with an email questionnaire that was sent after the woman had received her third and sixth quiz email. Information about pregnant women and their characteristics was obtained from Dutch registries to assess representativeness of the study population.

Results

About 8% of the pregnant women in the Netherlands enrolled in the program. Immigrants were underrepresented, and women with a low level of education seemed to be slightly underrepresented. Most women knew about the program from a promotional email sent by the organization (32%), followed by the Internet (22%) and midwives (16%). Women with little education were more often inactive users of the program than were highly educated women (15% vs 11%, P < .001), whereas highly educated women were more often very active users compared with women with little education (25% vs 20%, P< .001). However, women with less education were more likely than women with more education to have a high appreciation of the program after receiving three quiz emails (52% vs 44%, P = .001).

Conclusions

In this real-life setting, pregnant women can be reached through an email-based health promotion program. Selective engagement by education level remains a challenge.     

Chromosomal deletion unmasking a recessive disease: 22q13 deletion syndrome and metachromatic leukodystrophy

A deletion on one chromosome and a mutant allele on the other may cause an autosomal recessive disease. We report on two patients with mental retardation, dysmorphic features and low catalytic activity of arylsulfatase A. One patient had a pathogenic mutation in the arylsulfatase A gene ( ARSA ) and succumbed to metachromatic leukodystrophy (MLD). The other patient had a pseudoallele, which does not lead to MLD. The presenting clinical features and low arylsulfatase A activity were explained, in each patients, by a deletion of 22q13 and, thereby, of one allele of ARSA .     

Factors influencing the regional haemodynamic responses to methanandamide and anandamide in conscious rats

Background and purpose:

In vitro evidence suggests that metabolism of anandamide by cyclooxygenase-2 (COX-2) may be more important when the primary metabolic pathway [i.e. fatty acid amide hydrolase (FAAH)] is inhibited. Thus, the first aim of the present study was to assess the effects of COX-2 and/or FAAH inhibition, on the cardiovascular actions of anandamide. The second aim was to compare the effects of anandamide with those of the metabolically stable analogue (i.e. methanandamide) and investigate mechanisms involved in responses to the latter in conscious rats.

Experimental approach:

Rats were chronically instrumented for recording blood pressure, heart rate and renal, mesenteric and hindquarters vascular conductances in the freely moving state.

Key results:

Inhibition of FAAH with URB597 (cyclohexycarbamic acid 3′-carbamoyl-biphenyl-3-yl-ester) augmented the haemodynamic actions of anandamide, but there was no effect of COX-2 inhibition with parecoxib, either in the absence or the presence of URB597. Methanandamide caused CB₁ receptor-mediated renal and mesenteric vasoconstriction and evoked β₂-adrenoceptor-mediated hindquarters vasodilatation.

Conclusions and implications:

No evidence for an involvement of COX-2 in the systemic cardiovascular actions of anandamide could be demonstrated. Vasoconstrictor actions of methanandamide were shown to involve CB₁ receptors, whereas no involvement of CB₁ receptors in such actions of anandamide has been shown. However, β₂-adrenoceptor-mediated hindquarters vasodilatation, independent of CB₁ receptors, observed here with methanandamide, has previously been seen with anandamide and differs from previous results with other synthetic cannabinoids for which the response was CB₁ receptor-dependent. Thus, mechanisms underlying the cardiovascular actions of endocannabinoids and synthetic analogues appear to be agonist-specific.     

骨盆骨折合并尿道断裂的早期手术治疗

目的探讨骨盆骨折合并尿道断裂的早期手术方法及其治疗效果。方法自1995年1月至2005年1月,共收治骨盆骨折合并尿道断裂患者25例。根据Tile的分型方法,骨盆稳定型损伤1例,旋转不稳定型损伤17例,旋转及垂直均不稳定型损伤7例。尿道完全断裂23例、部分断裂2例。手术方法包括：（1）急诊尿道吻合、尿道会师部分吻合、尿道会师、尿道阴道贯通伤修补,同期行骨盆骨折开放复位内固定术9例。（2）急诊尿道会师,延期（7—21d）行骨盆骨折切开复位内固定术10例。（3）急诊膀胱造瘘,限期（3～21d）行尿道会师及骨盆骨折切开复位内固定术6例。结果术后随访6～120个月,平均34个月。骨盆损伤根据Majeed的疗效标准,优17例,良5例,可3例。尿管拔除后,19例（76％）患者排尿通畅,最大尿流率平均为18．6mL／s,排泄性尿路造影示尿道断端对位良好,瘢痕平均长度为0．51cm;5例（20％）出现不同程度的排尿困难,须定期扩张尿道或改行其他手术;1例（4％）女性患者不能控制排尿,须进一步治疗。术后耻骨上原发软组织撕脱伤感染伴耻骨后脓肿形成1例,后尿道狭窄5例,阳痿3例,尿失禁1例。结论骨盆骨折的早期复位和有效固定是实现“无张力尿道修复”的解剖基础。