Evaluation of the chronic toxicity and oncogenicity of N,N-diethyl-m- toluamide (DEET)

Chronic toxicity and/or oncogenicity studies were conducted in rats, mice, and dogs with the insect repellent DEET. DEET was mixed in the diet and administered to CD rats for two years at concentrations that corresponded to dosage levels of 10, 30 or 100 mg/kg/day for males and 30, 100, or 400 mg/kg/day for females; to CD-1 mice for 18 months at dosage levels of 250, 500, or 1000 mg/kg/day; and to dogs for one year, via gelatin capsules, at dosage levels of 30, 100, or 400 mg/kg/day. In the rodent studies, each group consisted of 60 animals of each sex, and two concurrent independent control groups, each containing 60 animals/sex were included in each study. Each group in the dog study consisted of four male and four female dogs and one control group was included in the study. Treatment-related effects were observed at the highest dose level in all three studies. For rats, the effects included decreases in body weight and food consumption and an increase in serum cholesterol in females only. In mice, the effects observed were decreases in body weight and food consumption in both sexes. The effects observed in dogs included increased incidences of emesis and ptyalism, and levels of transient reduction in hemoglobin and hematocrit, increased alkaline phosphatase (males only), decreased cholesterol, and increased potassium. One male dog in the high-dose group also exhibited ataxia, tremors, abnormal head movements, and/or convulsions on several occasions during the study. The highest no- observed-effect levels (NO-ELs) for rats, mice and dogs were determined to be 100, 500, and 100 mg/kg/day, respectively. No specific target organ toxicity or oncogenicity was observed in any of the studies.      

Dopa-responsive dystonia in British patients: new mutations of the GTP- cyclohydrolase I gene and evidence for genetic heterogeneity

Dopa-responsive dystonia (DRD) was originally described in a series of Japanese patients, but is now increasingly recognized in other countries. Recently the GTP cyclohydrolase I (GTPCH) gene was isolated as the first causative gene for dopa-responsive dystonia (DRD). Mutations were identified in three Japanese families with autosomal dominantly inherited DRD and in one sporadic Japanese patient. Characterisation of the exon-intron boundaries of this gene has now allowed the analysis of mutations at the level of genomic DNA. Amplifying all six exons, we analyzed the GTPCH gene in nine British families with 33 affected family members and in three sporadic cases and found six new mutations. Only point mutations were found, causing a stop codon in one family and an amino acid change in highly conserved regions of the gene in a further four families and in one sporadic case. None of these mutations were detected more than once and none of the mutations previously described were found in our patients. No mutations were identified in four families and in two sporadic cases.      

1141635071Suppressor of Cytokine Signalling 3 (SOCS3) controls trophoblast invasion and proliferation

Preterm birth is a major cause of perinatal morbidity and mortality. Intrauterine infection/inflammation is associated with a majority of preterm labor and birth cases. Despite decades of studies recognizing a strong association between infection/inflammation and preterm birth, no effective method of preventing infection-induced premature labor and delivery is yet available. Importantly, the mechanisms by which intrauterine infection/inflammation may contribute to preterm birth are not known. Based on our observations with human gestational tissue to highlight the role of IL-10 in normal and comprimised pregnancy outcomes, we have performed experiments with syngeneic and allogeneic pregnant IL-10^-/- mice or congenic wild type mice. Pregnancy outcomes were assessed in response to i.p. administration of low doses of lipopolysacchade (LPS) on gd 14. The mice were allowed to deliver or were sacrificed on gd 16 for isolation of uterine immune cells for functional studies or collected tissue for histological analysis. Attempts were made to prevent preterm parturition. LPS-treated IL-10^-/-, but not wild type mice, displayed a significant acceleration in time of delivery, on gd 16.5 compared to gd 19.6 for wild type controls. The premature delivery observed in LPS-treated IL-10^-/- mice was associated with an increase in the number of uterine NK (uNK) cells. These cells also displayed a dramatic infiltration of the placenta with a perivascular localization. uNK cells appear to be responsible for the induction of preterm birth in these mice as depletion of NK cells completely restored normal length of gestation. Moreover, neutralization TNF-α also rescued the premature delivery. Taken together, our results for the first time demonstrate that IL-10 deficiency and uterine NK cell cytotoxic activation link intrauterine inflammation to preterm parturition.     

In-service training with videotape is useful in teaching transfusion medicine principles

BACKGROUND: Failure to follow the basics of patient identification caused the ABO-incompatible transfusion and death of an anesthetized patient. An investigation found that the medical center's transfusion policy, while adequate, was not being disseminated uniformly to all personnel. STUDY DESIGN AND METHODS: With the help of the hospital's medical media department, a 23-minute videotape was produced emphasizing the importance of patient identification during phlebotomy and blood administration. Each department involved in blood transfusion was separately trained for a total of 182 persons trained. To assess whether learning had occurred, a 10-question quiz was administered both before and after the video was presented. A one-tailed t test was performed, and p < 0.05 was considered significant. RESULTS: The overall pre-video test mean was 8.0 and the post-video test mean was 9.5. The difference was highly significant at p < 0.00005. Except for the Transfusion Medicine Service, which had a perfect score on the pre- video test, all departments improved their scores with p values ranging from less than 0.00005 to 0.014. CONCLUSION: This study demonstrates that learning did occur. Videotape is useful for in-service training and can be used for teaching on a variety of topics in transfusion medicine.     

Frequency and patterns of abnormality detected by iodine-123 amine emission CT after cerebral infarction

Single photon emission computed tomography (SPECT) was performed in 31 patients with cerebral infarction and 13 who had had transient ischemic attacks, using iodine-123-labeled N,N,N'-trimethyl-N'-(2-hydroxyl-3-methyl-5-iodobenzyl)-1,3-propanediamin e (I-123-HIPDM) as the radiopharmaceutical. SPECT scans were compared with computed tomographic (CT) scans. SPECT was as sensitive as CT in detecting cerebral infarction (94% vs. 84%). The abnormalities were larger on the SPECT scans than on the CT scans in 19 cases, equal in seven, and smaller in five (SPECT abnormalities greater than or equal to CT abnormalities in 86% of cases). Fifteen of 30 patients with hemispheric infarction had decreased perfusion (decreased uptake of I-123-HIPDM) to the cerebellar hemisphere contralateral to the cerebral hemisphere involved by the infarction (crossed cerebellar diaschisis). Nine of these 15 patients had major motor deficits, while only one of the 15 without crossed cerebellar diaschisis had a major motor deficit.     

Post-traumatic abnormalities of the pubic bone simulating malignancy

Three cases are presented in which unusual healing patterns of pubic features simulated malignant processes. Consideration of trauma as an etiologic factor in such cases may obviate the need for extensive clinical and histologic evaluation.     

皮炎消净饮I号冲剂治疗异位性皮炎的实验研究

目的：研究皮炎消净饮I号冲剂（PYXJY1）治疗异位性皮炎（AD）的作用机理。方法：①动物实验：二硝基氯苯（DNCB）所致豚鼠耳肿试验,致敏处真皮内单核细胞和淋巴细胞聚集试验;醋酸所致小鼠腹腔毛细血管通透性增加试验。②实验室检测：单克隆抗体免疫荧光标记法检测AD患有治疗前后的CD4／CD8（TH／Ts）水平。结果：PYXJY1可明显抑制二硝基氯苯所致豚鼠耳肿胀及其真皮内单核细胞和淋巴细胞聚集,抑制醋酸所致小鼠腹腔毛细血管通透性的增加,作用与氢化可的松相似。使AD患者升高的CD4／CD8降低至正常。结论：PYXJY1具有良好的抗炎和迟发变态反应作用,并可调节AD患者CD4／CD8水平,对AD有较好的治疗效果。