A New Variant of Hereditary Hemolytic Anemia With Stomatocytosis and Erythrocyte Cation Abnormality

A new variant of congenital hemolyticanemia associated with stomatocytosis,reticulocytosis, decreased osmotic fragility, type I autohemolysis and shortened erythrocyte survival without specific splenic sequestration was discoveredin three siblings of Swiss-German ancestry. Increased intracellular sodium(two to three times normal) and slightlydecreased intracellular potassium weredetected. Total sodium efflux was eight-fold greater than normal but total potassium influx was normal and ouabain-sensitive potassium influx was decreased.The ouabain-sensitive sodium efflux:potassium influx ratio was 26:1 ratherthan the 3:2 ratio noted in normal cells.The consanguineous parents, four othersiblings, and 44 other family membershad mild stomatocytosis, reticulocytosis,and, when studied, decreased osmoticfragility, increased autohemolysis, intermediate abnormalities of cation content,cation flux, and moderate shortening oferythrocyte survival. Autosomal dominant inheritance was suggested. Noabnormalities of RBC enzymes, hemoglobin or lipids were observed. No abnormalities of membrane protein weredetected on acrylamide gel. Substratedepletion of these hypermetabolic cellsresulted in intracellular dehydrationwith potassium loss in excess of sodiumgain and decreased deformability. Although the exact nature of the defectresponsible for hemolysis is unknown,this syndrome differs from other hereditary hemolytic anemias associated withstomatocytosis.

Submitted on December 21, 1970 Revised on March 16, 1971 Accepted on March 29, 1971     

Enhanced Bone Regeneration Using Porcine Small Intestinal Submucosa

Small instestinal submucosa (SIS) is an easily produced material that has been used experimentally for tissue engineering. To evaluate the ability of SIS to facilitate bone growth within a long-bone defect, a segment of the radius was surgically removed in adult, female Sprague-Dawley rats. The defect was either left unfilled or implanted with SIS, demineralized cortical bone (DMCB), or ovalbumin. The defect was evaluated radiographically and histologically after 3, 6, 12, and 24 weeks. Tissue remodeling within the defect was evident by week 3 in SIS- and DMCB-treated rats. Filling was characterized initially by infiltration of mononuclear cells and extracellular material in SIS-implanted rats and multifocal remodeling bone particles and cartilage formation in DMCB implanted rats. Cartilage was observed as early as 3 weeks and bone as early as 6 weeks in SIS-implanted rats. Filling of the defect arose from multiple foci in DMCB-implanted rats, but was contiguous with and parallel to the ulnar shaft in SIS-implanted rats, suggesting that defect repair by SIS may be conductive rather than inductive. Rats in which the defect was left unfilled demonstrated slow but progressive filling of the defect, characterized by mononuclear cell infiltrates and fibrous extracellular material. In summary, SIS facilitated rapid filling of a longbone defect. These results suggest that SIS may be useful as a bone repair material.     

广州市荔湾区青少年脊柱侧凸患病率的调查研究

目的了解广州市荔湾区青少年脊柱侧凸的患病率。方法 2011年7月~2012年1月对荔湾区8351名7~15岁在校中小学生进行了脊柱侧凸普查,应用脊柱侧凸两检法（体检、X线照片）,体检阳性或可疑阳性者到医院照脊柱全长正侧位X片,采用Cobb法测量,Cobb角≥10°诊断为脊柱侧凸。结果一检阳性结果 175名（2.1%）,二检阳性为85名（1.02%）,男性31名,女性54名,男∶女患病率比为1∶1.76,其中特发性脊柱侧凸81名,占95.3%,先天性侧凸3名,神经肌肉源性1名。结论荔湾区中小学生脊柱侧凸发病率为1.02%,通过普查,可以早发现、早诊断青少年脊柱侧凸,及时选择适当方法进行治疗。     

几种表面活性剂对P-gp底物罗丹明123经肠黏膜透过性的影响

 目的观察低浓度表面活性剂聚氧乙烯蓖麻油,Labrasol和聚山梨酯80对肠黏膜P-gp的调控作用。方法使用体外扩散池法评价罗丹明123(R123)经空肠、回肠和结肠黏膜的经时经吸收方向和分泌方向的透过量和透过系数(P_app),并测定不同浓度表面活性剂对R123和荧光素钠(CF)经肠黏膜透过性的影响。R123和CF在接受室中的浓度用荧光分光光度法测定。结果R123经肠道黏膜的透过性存在部位差,即以空肠、回肠和结肠的次序透过性依次减少。另一方面,R123经肠道分泌方向的透过性显著地高于其吸收方向的透过性。低浓度的CEL和Labrasol可显著增强R123经吸收方向的透过性,减少经分泌方向的透过性;而低浓度的聚山梨酯80可显著增强R123经吸收方向的透过性,但对经分泌方向的透过性无显著影响。但实验浓度的表面活性剂对CF的肠道转运没有影响。结论低浓度的聚氧乙烯蓖麻油、Labrasol和聚山梨酯80可通过对P-gp功能的抑制而用于改善受P-gp介导药物的吸收,有望提高此类药物的口服生物利用度。     

蒙成药嘎日迪-5味丸方源考证及其现代研究进展

目的：对蒙药嘎日迪-5味丸的方源考证及其现代研究进展进行综述,为该复方的进一步开发与利用提供依据。方法:采用蒙医文献研究与考证、文献综述方法,从基源、方解、临床应用以及化学成分等方面对蒙药嘎日迪-5味丸研究现状进行总结和分析。结果:蒙药嘎日迪-5最早收载于藏医学家宇妥·云丹贡布于公元8世纪下旬撰写的藏医经典著作《四部医典》,属于蒙药、藏药传统验方,由诃子、麝香、草乌（制）、石菖蒲、木香配伍组成,其他处方都是在使用的过程中,根据临床应用演变而来,具有杀黏、止痛、消肿、燥协日乌素功效。蒙医临床用于治疗黏引起的瘟疫热症、黏虫病、黏性刺痛、维生素C缺乏病、风湿、白喉炭疽、瘰疬疮疡、正偏头痛、疥癣等疾病,疗效显著。结论:蒙药嘎日迪-5方出自《四部医典》,属传统验方,对瘟疫热症、黏虫病、黏性刺痛等黏性疾病疗效显著,具有潜在的开发利用价值。     

Dorsal lunate tilt (DISI configuration): sign of scaphoid fracture displacement

Excessive dorsiflexion (dorsal tilting) of the lunate on a lateral wrist radiograph can be an important sign of carpal injury. Lunate dorsiflexion is a well-recognized sign of an intercarpal ligamentous injury pattern known as dorsal intercalated segment instability (DISI). It is less well recognized that excessive dorsal tilting of the lunate (DISI configuration) can also be produced by displacement of a scaphoid waist fracture. Since the management and prognosis of displaced scaphoid fractures may be quite different from those for nondisplaced fractures, radiologists can make an important contribution by recognizing dorsal tilting of the lunate and appreciating that it may be an important, indirect sign of scaphoid fracture displacement, which may not be directly visualized with standard wrist radiography. In this setting, computed tomography or complex motion tomography may be helpful for further evaluation of the scaphoid fracture.     

Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung

Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.      

High throughput parallel analysis of hundreds of patient samples for more than 100 mutations in multiple disease genes

As more mutations are identified in genes of known sequence, there is a crucial need in the areas of medical genetics and genome analysis for rapid, accurate and cost-effective methods of mutation detection. We have developed a multiplex allele-specific diagnostic assay (MASDA) for analysis of large numbers of samples (> 500) simultaneously for a large number of known mutations (> 100) in a single assay. MASDA utilizes oligonucleotide hybridization to interrogate DNA sequences. Multiplex DNA samples are immobilized on a solid support and a single hybridization is performed with a pool of allele-specific oligonucleotide (ASO) probes. Any probes complementary to specific mutations present in a given sample are in effect affinity purified from the pool by the target DNA. Sequence-specific band patterns (fingerprints), generated by chemical or enzymatic sequencing of the bound ASO(s), easily identify the specific mutation(s). Using this design, in a single diagnostic assay, we tested samples for 66 cystic fibrosis (CF) mutations, 14 beta-thalassemia mutations, two sickle cell anemia (SCA) mutations, three Tay-Sachs mutations, eight Gaucher mutations, four mutations in Canavan disease, four mutations in Fanconi anemia, and five mutations in BRCA1. Each mutation was correctly identified. Finally, in a blinded study of 106 of these mutations in > 500 patients, all mutations were properly identified. There were no false positives or false negatives. The MASDA assay is capable of detecting point mutations as well as small insertion or deletion mutations. This technology is amenable to automation and is suitable for immediate utilization for high-throughput genetic diagnostics in clinical and research laboratories.      

bcl-2 transgene expression promotes survival and reduces proliferation of CD3-CD4-CD8- T cell progenitors

Proliferative expansion and apoptotic cell death play prominent roles in T cell development. The molecular control of cell cycle progression and apoptosis appear to be inter-connected since the Bcl-2 protein can inhibit apoptosis and slow cell cycle progression in cortical thymocytes and mature T cells, particularly during the transition from the quiescent state into the cell cycle. Here the impact of bcl-2 transgene expression on CD3-CD4-CD8- T cell progenitors was assessed. Bcl-2 enhanced the survival of these progenitors at all of the four major differentiation stages, CD25- CD44+ (pro-T1), CD25 + CD44+ (pro- T2), CD25 + CD44- (pro-T3) and CD25-CD44- (pro-T4). However, it reduced cell cycling and slowed turnover only in the pro-T4 subset. From an analysis of bcl-2 transgenic mice expressing a TCR transgene or bearing a mutation in the scid or rag-1 gene we conclude that Bcl-2 inhibits proliferation only of T cell progenitors that are activated via the pre- TCR, not those stimulated via c-Kit and the IL-7 receptor.      

Evaluation of the In Vivo Activity of Different Concentrations of Clerodendrum Umbellatum Poir Against Schistosoma Mansoni Infection in Mice

Clerodendrum umbellatum Poir (Verbenaceae) is traditionally used in Cameroon for the treatment of many diseases including intestinal helminthiasis. This study was undertaken to assess the in vivo antischistosomal activity of its leaves aqueous extract on a Schistosoma mansoni mice model and to determine the most effective dose of this extract. Mice showing a patent infection of S. mansoni were daily treated with C. umbellatum leaves aqueous extract at the doses of 40, 80 or 160 mg/kg body weight for 14 days. Seven days after administration of the extract, schistosomicidal activity was evaluated on the liver and spleen weights, faecal eggs releasing, liver egg count and worm burden. Treatment using C. umbellatum leaves aqueous extract resulted in an important reduction in faecal egg output by 75.49 % and 85.14 % for 80 mg/kg and 160 mg/kg of the extract respectively. These reduction rates did not differ significantly from the 100 % obtained in the group of infected mice treated with 100 mg/kg of praziquantel. C. umbellatum leaves aqueous extract was lethal to S. mansoni worm. A 100 % reduction rate was recorded in the group of infected mice treated with 160 mg/kg of the extract, as well as in praziquantel-treated mice. An amelioration of the hepatosplenomegaly was noticed in both the extract-treated mice and the praziquantel-treated mice. From these results, we can conclude that C. umbellatum leaves aqueous extract demonstrated schistosomicidal properties in S. mansoni model at doses of at least 80 mg/kg body weight.