Actual asthma control in a paediatric outpatient clinic population: Do patients perceive their actual level of control?

Several epidemiological studies described poor asthma control in children. However, the diagnosis of childhood asthma in these studies is uncertain, and asthma control in children of an outpatient clinic population during treatment by a paediatrician is unknown. (1) to investigate the hypothesis that asthma control in a paediatric outpatient clinic population is better than epidemiological surveys suggest; (2) to find possible explanations for suboptimal asthma control. Asthmatic children aged 6–16 years, known for at least 6 months by a paediatrician at the outpatient clinic, were selected. During a normal visit, both the responsible physicians and parent/children completed a standardised questionnaire about asthma symptoms, limitation of daily activities, treatment, asthma attacks and emergency visits. Overall, excellent asthma control of 8.0% in this study was not significantly better than of 5.8% in the European AIR study (Chi‐square, p = 0.24). Separate GINA goals like minimal chronic symptoms and no limitation of activities were better met in our study. Good to excellent controlled asthma was perceived by most children/parents (83%), but was less frequently indicated by the paediatrician (73%), or by objective criteria of control (45%) (chi‐square, p = 0.0001). The agreement between patient‐perceived and doctor assessed control was low, but improved in poorly controlled children. Patients were not able to perceive the difference between ‘excellent asthma control’ and ‘good control’ (p = 0.881).Too little children with uncontrolled disease got step‐up of their asthma treatment. Although separate GINA goals like ‘minimal chronic symptoms’ and ‘no limitation of activities’ were significantly better in our study, overall, asthma control in this outpatient clinic population, treated by a paediatrician, was not significantly better than in the European AIR study. Poorly controlled disease was related to several aspects of asthma management, which are potentially accessible for improvements.     

Blood transfusion and postoperative infection in orthopedic patients

Adverse effects of the transfusion of homologous blood on tumor recurrence and resistance to bacterial infection have been reported previously, but the findings are inconclusive. A retrospective review of patients undergoing orthopedic surgery was conducted, and the rate of the postoperative infectious complications was compared among those receiving homologous blood, autologous blood, both types, or no transfusion support. An overall postoperative infection rate of 6.1 percent was observed: 6.9 percent among persons receiving homologous blood, 5.0 percent among those receiving autologous blood, 11.9 percent among those receiving both homologous and autologous blood, and 4.9 percent among those not receiving transfusions (p = 0.37). Among patients receiving homologous blood, a subset of 15 patients received homologous whole blood and had an infection rate of 20 percent. Significant predictors of postoperative infection included increasing age, spinal surgery, high admission hematocrit, and greater time in surgery. Of factors relating to transfusion, only the use of homologous whole blood was a significant predictor of postoperative infection, which suggests a detrimental effect of homologous plasma. It can be concluded that, in this group of patients undergoing relatively nontraumatic surgery, several variables that are not related to transfusion, as well as the use of homologous whole blood, were significant predictors of postoperative infection.     

Negative selection during the peripheral immune response to antigen

Thymic selection depends on positive and negative selective mechanisms based on the avidity of T cell interaction with antigen-major histocompatibility complex complexes. However, peripheral mechanisms for the recruitment and clonal expansion of the responding T cell repertoire remain obscure. Here we provide evidence for an avidity-based model of peripheral T cell clonal expansion in response to antigenic challenge. We have used the encephalitogenic, H-2 A(u)-restricted, acetylated NH(2)-terminal nonameric peptide (Ac1-9) epitope from myelin basic protein as our model antigen. Peptide analogues were generated that varied in antigenic strength (as assessed by in vitro assay) based on differences in their binding affinity for A(u). In vivo, these analogues elicited distinct repertoires of T cells that displayed marked differences in antigen sensitivity. Immunization with the weakest (wild-type) antigen expanded the high affinity T cells required to induce encephalomyelitis. In contrast, immunization with strongly antigenic analogues led to the elimination of T cells bearing high affinity T cell receptors by apoptosis, thereby preventing disease development. Moreover, the T cell repertoire was consistently tuned to respond to the immunizing antigen with the same activation threshold. This tuning mechanism provides a peripheral control against the expansion of autoreactive T cells and has implications for immunotherapy and vaccine design.     

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。     

Mucopolysaccharidosis type IVA (morquio syndrome): A clinical review

Summary Patients with MPS IV have a clinical disorder quite different from other MPS conditions. The major treatment issue revolves around the prevention of cervical myelopathy, although the other aspects of this multisystem disease should not be forgotten. Management is inevitably multidisciplinary and the paediatrician should play a lead role in the coordination of services for affected patients.The timing of occipito-cervical fusion and the selection of patients for this procedure remain unclear. A prophylactic approach to surgery is suggested in this review, although it is by no means clear that all patients will invariably develop cervical myelopathy if left untreated.Parents of affected children need considerable support in dealing with the affected child and the children themselves need help to try to come to terms with their severe physical disabilities. The Society for Mucopolysaccharide Diseases (55 Hill Avenue, Amersham, Bucks HP6 5BX, UK) has offered many parents and affected individuals considerable help as well as raising significant sums for research.Finally, it is important to remember the genetic nature of the disease and the possibility of prenatal diagnosis in subsequent pregnancies.     

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.