抗生素在流感大流行中的应用

随着禽流感病毒H5N1的不断蔓延,越来越有可能发生人类流感的大流行。如果现在发生流感的大流行,不仅还没有有效的疫苗,而且还可能造成抗病毒药物的缺乏。目前尚没有证据表明抗流感药物神经氨酸酶抑制剂(neuraminidaseinhibitor对)禽流感和流感大流行的病毒有效,给予神经氨酸酶抑制剂后,感染H5N1禽流感病毒的患者的死亡率仍然很高。而且流感病毒的耐药会进一步限制抗病毒药物的疗效。假如继发性细菌感染是流感常见且重要的致命性并发症,那么抗生素在人类流感大流行中将占有重要的一席地位。     

Macroscopic evaluation of rectal cancer resection specimen: clinical significance of the pathologist in quality control.

PURPOSE: Quality assessment and assurance are important issues in modern health care. For the evaluation of surgical procedures, there are indirect parameters such as complication, recurrence, and survival rates. These parameters are of limited value for the individual surgeon, and there is an obvious need for direct parameters. We have evaluated criteria by which pathologists can judge the quality or completeness of the resection specimen in a randomized trial for rectal cancer. PATIENTS AND METHODS: The pathology reports of all patients entered onto a Dutch multicenter randomized trial were reviewed. All participating pathologists had been instructed by workshops and videos in order to obtain standardized pathology work-up. A three-tiered classification was applied to assess completeness of the total mesorectal excision (TME). Prognostic value of this classification was tested using log-rank analysis of Kaplan-Meier survival curves using the data of all patients who did not receive any adjuvant treatment. RESULTS: Included were 180 patients. In 24% (n = 43), the mesorectum was incomplete. Patients in this group had an increased risk for local and distant recurrence, 36.1% v. 20.3% recurrence in the group with a complete mesorectum (P =.02). Follow-up is too short to observe an effect on survival rates. CONCLUSION: A patient's prognosis is predicted by applying a classification of macroscopic completeness on a rectal resection specimen. We conclude that pathologists are able to judge the quality of TME for rectal cancer. With this direct interdisciplinary assessment instrument, we establish a new role of the pathologist in quality control.     

A Phase I study with an anti-CD30 ricin A-chain immunotoxin (Ki-4.dgA) in patients with refractory CD30+ Hodgkin's and non-Hodgkin's lymphoma.

Ki-4.dgA is an anti-CD30 immunotoxin (IT) constructed by coupling the monoclonal antibody Ki-4 via a sterically hindered disulfide linker to deglycosylated ricin A-chain. This IT was efficacious in vitro and in SCID mice with disseminated human Hodgkin's lymphoma. Accordingly, a Phase I trial in patients (pts) with Hodgkin's lymphoma was designed. The objectives of this Phase I trial were to determine the maximum tolerated dose, the dose-limiting toxicities, pharmacokinetics, and antitumor activity. Seventeen pts with relapsed CD30+ lymphoma were treated with escalating doses (5, 7.5, or 10 mg/m(2)/cycle) of the IT as four bolus infusions on days 1, 3, 5, and 7 for one to three cycles. All of the pts had progressive disease and were heavily pretreated. Nine had primary progressive disease and 14 had advanced disease with massive tumor burdens. The mean age was 35 years (24-52 years). Peak serum concentrations of the intact IT varied from 0.23 to 1.1 microg/ml. Side effects and dose-limiting toxicities were related to vascular leak syndrome, i.e., decreases in serum albumin, edema, weight gain, hypotension, tachycardia, myalgia, and weakness. The maximum tolerated dose was 5 mg/m(2). Seven of 17 (40%) pts made human antiricin antibodies (> or =1.0 microg/ml), and 1 pt developed human antimouse antibodies (> or =1.0 microg/ml). Clinical response in the 15 evaluable pts included 1 partial remission, 1 minor response, and 2 stable diseases. In conclusion, the IT was less well tolerated than other ITs of this type. This might be because of the low number of CD30+ peripheral blood mononuclear cells, and in part because of binding of the IT to soluble CD30 antigen and the resulting circulation of IT/sCD30 complexes.     

Children with cochlear implants who live in monolingual and bilingual homes.

OBJECTIVE: To determine if exposure to a second language impacts the ability of children with cochlear implants to develop spoken English skills. STUDY DESIGN: Matched-pairs comparison of postoperative speech perception and speech/language data of children from monolingual and bilingual homes with cochlear implants. SETTING: Tertiary medical facility. SUBJECTS: Twelve matched pairs of children with unilateral cochlear implants who reside in monolingual or in bilingual homes. Pairs were matched for age of implantation, cochlear anatomy, educational setting, and device type. All subjects received their implant before the age of 6 years. INTERVENTION: Subjects participated in routine speech perception and speech and language assessments at various postimplantation time intervals. MAIN OUTCOME MEASURES: Matched-pairs t tests and mixed-model analyses were used to evaluate and compare scores obtained by the 2 groups on the Peabody Picture Vocabulary Test, The MacArthur-Bates Communicative Development Inventory: Words and Gestures, The Oral and Written Language Scales, The Infant-Toddler Meaningful Auditory Integration Scale, and the Student Oral Language Observation Matrix. RESULTS: No significant differences were found between the scores of children living in bilingual homes when compared with the scores obtained by children living in monolingual homes at any interval tested. CONCLUSION: This study supports the belief that exposure to a second language at home does not impair primary language acquisition for some young children with cochlear implants. The study suggests that some children with cochlear implants can learn multiple spoken languages and that parents of such children do not need to avoid using a minority language with their child who has a cochlear implant.     

Motor performance and functional ability in preschool- and early school-aged children with Juvenile Idiopathic Arthritis: a cross-sectional study

Objective  

To describe the level of motor performance and functional skills in young children with JIA.     

The dopamine receptor D4 7‐repeat allele and prenatal smoking in ADHD‐affected children and their unaffected siblings: no gene–environment interaction

Background: The dopamine receptor D4 (DRD4) 7‐repeat allele and maternal smoking during pregnancy are both considered as risk factors in the aetiology of attention deficit hyperactivity disorder (ADHD), but few studies have been conducted on their interactive effects in causing ADHD. The purpose of this study is to examine the gene by environment (G×E) interaction of the DRD4 7‐repeat allele and smoking during pregnancy on ADHD and oppositional behavior in families from the International Multicenter ADHD Genetics project; and further, to test the hypothesis that the direction of effect of the DRD4 7‐repeat allele differs between ADHD affected and unaffected children. Methods: Linear mixed models were used to assess main and interactive effects of the DRD4 7‐repeat allele and smoking during pregnancy in 539 ADHD‐affected children and their 407 unaffected siblings, aged 6–17 years. Results: There was some evidence pointing to differential effects of the DRD4 7‐repeat allele on ADHD and oppositional symptoms in the affected (fewer symptoms) and unaffected children (increasing ADHD symptoms of teacher ratings). Affected children were more often exposed to prenatal smoking than unaffected children. There were limited main effects of prenatal smoking on severity of symptoms. Given the number of tests performed, no indication was found for G×E interactions. Conclusion: Despite the large sample size, no G×E interactions were found. The impact of the DRD4 7‐repeat allele might differ, depending on affected status and rater. This finding is discussed in terms of differences in the activity of the dopaminergic system and of different genes involved in rater‐specific behaviors.     

幽门螺杆菌黏唾液酸黏附素疫苗治疗小鼠幽门螺杆菌感染

目的:利用人类幽门螺杆菌(H. pylori)感染的小鼠模型研究唾液酸黏附素疫苗治疗H. pylori感染的作用.方法:把已感染H. pylori的小鼠分成4组,分别通过灌胃方法给予唾液酸黏附素100 μg加霍乱毒素CT 2 μg、单纯唾液酸黏附素100 μg、单纯CT 2 μg或PBS,1次/wk,共4次,治疗结束后4 wk处死动物,取胃粘膜行半定量细菌培养检查H. pylori情况.结果:治疗后各组H. pylori根除率分别为:唾液酸黏附素加CT组30%(3/10)、单纯唾液酸黏附素组、单纯CT组及PBS组根除率均为0%.差异有统计学意义.未根除H. pylori的小鼠,唾液酸黏附素加CT组H. pylori的定植密度明显低于其它3组(P＜0.05).结论:唾液酸黏附素能够作为H. pylori多价治疗疫苗的组分之一.