Cryptic structural lesions in refractory partial epilepsy: MR imaging and CT studies

Results of contrast material-enhanced computed tomography (CT) and T2-weighted spin-echo magnetic resonance (MR) imaging were correlated with pathologic findings in 25 patients treated surgically for refractory partial epilepsy. Of 12 lesions present, ten (83%) were detected by MR imaging and seven (58%) by CT scanning. Of nine low-grade gliomas, eight were detected by MR imaging and four by CT scanning. One posttraumatic scar and one case of temporal lobe atrophy were better demonstrated by MR imaging. A small, thrombosed arteriovenous malformation was the only lesion detected by CT scanning but not by MR imaging. No lesions were detected in 13 patients with mild gliosis and one patient with a 1.2-cm grade 1 astrocytoma. Although more sensitive than CT for detection of structural lesions in patients with refractory partial epilepsy, MR imaging resulted in a 25% false-negative diagnostic rate when a repetition time of 2,000 msec and echo time of 60 msec were used. Multi-echo imaging with at least one long echo time may be needed to increase the sensitivity of MR imaging in these patients.     

Encapsidated adenovirus mini-chromosome-mediated delivery of genes to the retina: application to the rescue of photoreceptor degeneration

First (DeltaE1/E3) and second (DeltaE1+DeltaE2/E3/E4) generation adenovirus (Ad) vectors have been shown previously to be of limited use in the treatment of human genetic diseases due to the induction of a host cytotoxic T-cell mediated immune response against virally expressed genes. In addition, a limited cloning capacity of approximately 8 kb does not cater for the incorporation of large upstream sequences essential for regulated tissue-specific expression or inclusion of multiple gene-expression cassettes. In this study we have exploited our recently developed Ad-based vector, the encapsidated adenovirus mini-chromosome (EAM) from which all of the viral genes have been deleted. EAMs contain only the inverted terminal repeats required for replication and five cis -acting Ad encapsidation signals necessary for packaging. We have shown previously that EAMs can efficiently transduce a variety of cell types in vitro. In this study we demonstrate that EAMs can transduce and rescue cells from the neurosensory retina in vivo. EAM-mediated delivery of the beta subunit of cyclic GMP phosphodiesterase (PDE) cDNA to mice affected with retinal degeneration (rd) allows prolonged transgene expression and rescue of rod photoreceptor cells. RT-PCR analysis from the injected retina indicates that transgene products are present for at least 18 weeks post-injection. Both the alpha and beta subunits of PDE could be detected up to 90 days postnatal in EAM-injected rd retina by western analysis. A maximal PDE activity of 150 nm/min/mg was detected at 33 days postnatal. Examination of outer nuclear thickness showed significant differences up to 12 weeks post-injection. These results demonstrate an improved level of rescue over first-generation adenoviral vectors and suggest the possibility of successful EAM- mediated treatment of some retinal diseases in humans.      

Changes in symptom scores as a potential clinical endpoint for studies of cystic fibrosis pulmonary exacerbation treatment

Introduction: Symptom improvement was assessed as changes in the Chronic Respiratory Infection Symptom Score (CRISS) during intravenous antimicrobial exacerbation treatments among subjects from study NCT02109822.Methods: Median daily CRISS reduction (i.e., improvement) and covariates associated with CRISS reduction by Day 14 were assessed by logistic regression.Results: Among 173 subjects, median baseline CRISS was 49 [IQR 41, 56]; 93.6% had a CRISS reduction of ≥11 (minimal clinically important difference); median time to –11 reduction was 2 days [95% CI 2, 3]. The greatest median CRISS difference from baseline, on Day 17, was –26 [–29, –23]. Odds of –26 CRISS change by Day 14 were greater in subjects with higher baseline CRISS (P=.006) and younger ages (P=.041).Conclusions: CRISS response has good dynamic range and may be a useful efficacy endpoint for PEx interventional trials. The optimal use of CRISS change as an endpoint remains uncharacterized.     

Increased plasma thyroid stimulating hormone in treated congenital hypothyroidism: relation to severity of hypothyroidism, plasma thyroid hormone status, and daily dose of thyroxine

Plasma thyroid stimulating hormone (TSH) concentrations obtained during the first four years of treatment in 418 children with congenital hypothyroidism, identified by neonatal screening, were examined in relation to paired measurements of plasma thyroxine (n = 1945), free thyroxine (n = 836), triiodothyronine (n = 480), and free triiodothyronine (n = 231), and estimated daily dose of thyroxine at the time of blood sampling. Overall, plasma TSH was above 7 mU/l in 1280 out of 2960 samples (43%); the percentage was not related to severity of hypothyroidism at diagnosis. Mean values for thyroxine and free thyroxine, and to a lesser extent free triiodothyronine, were consistently lower in samples with TSH concentrations over 7 mU/l and this was the case in patients with either severe or less severe hypothyroidism. Raised TSH concentrations were also associated with lower mean doses of thyroxine (micrograms/kg/day) but here the mean doses of thyroxine in children with severe hypothyroidism were higher than in the children with less severe hypothyroidism. The mean dose of thyroxine associated with low/normal TSH values was highest in the first 6 months and fell progressively. Thyroxine dose was significantly related to thyroxine and free thyroxine concentrations but not to triiodothyronine and free triiodothyronine and the latter appeared to be of limited value as measures of plasma thyroid hormone status during treatment.     

瞬时性受体电位通道香草酸受体5、6与骨代谢的关系

目的:探讨瞬时性受体电位通道香草酸受体5、6与骨代谢的关系。资料来源:应用计算机检索PubMed数据库1999-01/2006-07相关瞬时性受体电位通道方面的文献,检索词“TRPV”,限定文献语言种类为English。资料选择:对资料进行初审,选取包括瞬时性受体电位通道香草酸受体5、6的文献,开始查找全文。纳入标准:对两者及瞬时性受体电位通道家族进行研究的文章。排除标准:研究内容局限于瞬时性受体电位通道香草酸受体1～4的文章。资料提炼:共检索到106篇关于瞬时性受体电位通道香草酸受体的文献,最终纳入30篇符合标准的文献。资料综合:瞬时性受体电位通道香草酸受体5、6是瞬时性受体电位通道超家族中的成员,是专门的上皮样钙离子通道。目前研究已经证明它们在肠道和肾脏等组织中有表达,并对跨细胞钙离子转运起着关键性调控作用。但在骨组织中表达情况相关报道较少,在骨代谢机制上的研究更少,本文针对目前两者与骨代谢的关系进行综述。结论:深入研究瞬时性受体电位通道香草酸受体5、6钙离子通道在骨代谢中的作用,对于那些与骨代谢相关疾病的治疗将能从分子水平上找到解决的方法。     

伊贝母中伊贝碱甙C的分离和结构鉴定

自吉林栽培的伊贝母(Fritillaria pallidiflora Schrenk)中分得一种新的甾体生物碱甙,命名为伊贝碱甙C(yibeinosideC)。根据红外、质谱、氢谱、碳谱、¹H-¹HCOSY和¹H-¹³CCOSY谱确定其结构为22,26-环亚胺胆甾-6-酮-3-O-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃半乳糖甙(1)。     

Human chorionic gonadotrophin-beta gene sequences in women with disorders of HCG production

Women with recurrent abortion, primary unexplained infertility, and gestational trophoblastic neoplasia (GTN) manifest disordered human chorionic gonadotrophin (HCG) secretion. Mutations in the HCG beta/luteinizing hormone (LH) beta gene complex could cause aberrant HCG production in these disorders. The purpose of this study was to determine whether HCG beta gene deletions occur in women with recurrent abortion or primary unexplained infertility, and whether HCG beta gene duplications are present in women with GTN. DNA was extracted from 10 patients with unexplained recurrent abortion, 10 patients with unexplained primary infertility, 12 patients with GTN, three partners of women with GTN, and 30 controls. Southern blots were constructed and hybridized with DNA probes for HCG beta-5 and the LH beta gene. No gene deletions were identified in patients with recurrent abortion or primary unexplained infertility. Likewise, no gene duplications were identified in women with GTN. A previously described Mbol restriction fragment length polymorphism (RFLP) was identified in both patients and controls. A new Pstl RFLP was also characterized, but was present in patients and controls. Deletion/duplication mutations in the HCG beta/LH beta gene complex do not appear to be common causes of aberrant HCG production in humans with these disorders.      

创伤与复苏:治疗创伤性凝血病需要特殊血液制品

民用创伤中心和部队战斗支持医院正在收治越来越多的严重损伤,他们常规挽救那些在二十年前无法医治的病人。最重要的进展是发展了“紧急”外科学———由于发生凝血病阻碍了正常解剖的恢复,这项技术的发展超越了常规的血库支持治疗。失控的凝血紊乱性出血是创伤后可预防的导致死亡的主要原因。在美国每年大约有1/10的人由于创伤需要医疗处理,其中1/100的人住院,大约1/1000由于创伤后紧急处理而输注了血液制品。2000年,美国马里兰的大学创伤性休克中心(UMSTC),5649人中8%的受伤病人入院后直接根据创伤情况输注红细胞,5%的输注血浆,3%的输注…