Keratan sulphate in rheumatoid arthritis, osteoarthritis, and inflammatory diseases.

Serum concentrations of antigenic keratan sulphate determined by an enzyme linked immunosorbent assay (ELISA) with a monoclonal antibody were studied in patients with rheumatoid arthritis (RA), osteoarthritis, ankylosing spondylitis, other inflammatory diseases, and a large control group of women without arthritis. Mean keratan sulphate concentrations were low in 117 women with RA compared with 227 female control subjects matched for age drawn from a community survey. There were significant correlations between serum keratan sulphate concentrations in patients with RA and serum C reactive protein and the erythrocyte sedimentation rate. Serum keratan sulphate concentrations were also low in 29 men and women with ankylosing spondylitis and 29 patients with arthritis and high concentrations of C reactive protein. In 98 women undergoing an operation for benign breast disease there were decreases in serum keratan sulphate concentrations after the operation which correlated with doses in serum C reactive protein. No differences were found in keratan sulphate concentrations in 137 women with osteoarthritis compared with controls. Within the group with osteoarthritis there were no differences for the various joint groups and there was no obvious correlation with radiographic severity or progression. These findings suggest serum keratan sulphate is unlikely to be useful as a diagnostic marker in osteoarthritis or RA but indicate a role for inflammation in the regulation of cartilage loss.     

Amnesia-reversal activity of a series of cyclic imides

A series of dihydro-1H-pyrrolizine-3,5(2H,6H)-diones were synthesized and evaluated for their ability to reverse electroconvulsive shock (ECS) induced amnesia in mice. Among the structure-activity relationships explored were the effects of ring size, the presence of heteroatoms (sulfur) in the ring system, and the introduction of alkyl substituents. The optimal ring size for the bicyclic system was 5.5 with dihydro-1H-pyrrolizine-3,5(2H,6H)-dione (3), although some activity was present in the corresponding 5.6 [hexahydro-3,5-indolizinedione (7)] and 6.6 [tetrahydro-2H-quinolizine-4,6(3H,7H)-dione (9)] analogues. Replacement of the C-1 carbon atom in compound 3 with a sulfur [dihydropyrrolo[2,1-b]thiazole-3,5(2H,6H)-dione (10)] abolished activity, and the introduction of methyl groups resulted in poorer biological profiles except when the substitution was made at the 7a position [dihydro-7a-methyl-1H-pyrrolizine-3,5(2H,6H)-dione (4)]. In several instances, hydrolysis of the parent bicyclic compound was carried out to furnish the corresponding lactam acids, which were further derivatized. Several exhibited interesting activity, especially the 5-oxo-2-pyrrolidinepropanoic acid derivatives such as 5-oxo-2-pyrrolidinepropanoic acid (12), 5-oxo-2-pyrrolidinepropanoic acid phenylmethyl ester (17), 5-oxo-2-pyrrolidinepropanoic acid (3-chlorophenyl)methyl ester (20), N-4-pyridyl-5-oxo-2-pyrrolidinepropanoic acid amide (25), and N-(2,6-dimethylphenyl)-5-oxo-2-pyrrolidinepropanoic acid amide (27). Compound 3 (CI-911; rolziracetam) was also observed to improve performance on a delayed-response task in aged rhesus monkeys and was selected for evaluation in cognitively impaired human subjects on the basis of its biological profile and a wide margin of safety in animals.     

The role of arthroscopic surgery in the evaluation of acute traumatic hemarthrosis of the knee

Eighty patients presented for evaluation with an acute traumatic hemarthrosis of the knee and negligible instability on clinical examination. All had an examination under general anesthesia followed by arthroscopy. Anatomical lesions were demonstrated in 71 of 80 knees (89%) including anterior cruciate ligament (ACL) disruption in 50 (62%). Twenty-nine of 50 patients (58%) with arthroscopically-demonstrated ACL injuries had associated meniscal tears. Fifteen (19%) demonstrated isolated meniscal tears and nine (11%) osteochondral fractures not detected by conventional roentgenograms. The frequent occurrence of injuries to other joint structures in conjunction with ACL injuries was remarkable. An acute traumatic hemarthrosis of the knee often masks significant lesions. Arthroscopy aids the orthopedic surgeon in determining the full extent of the intraarticular damage.     

Bird lung models show that convective inertia effects inspiratory aerodynamic valving

We assessed various aerodynamic factors which might influence inspiratory valve function in the avian lung. During inspiration, no flow enters the proximal segments of the ventrobronchi connecting the primary bronchus to cranial sacs. Instead, all flow in the primary bronchus continues through the mesobronchus. This pattern of flow past the ventrobronchi into the mesobronchus is called inspiratory aerodynamic valving. Introducing steady inspiratory flows into simplified plastic models of a bifurcation, we altered geometry, downstream resistance, flow rate and gas density while we measured the resulting flow partitioning between downstream branches. We found that these models did reproduce the inspiratory valving phenomenon. Gas flow rate, gas density and geometry upstream of the bifurcation played important roles in flow partitioning, but the geometry and branching angles of the ventrobronchi did not. These findings are consistent with the idea that convective inertia of the inspiratory gas stream promotes preferential axial flow (Butler et al., 1988) and may be the principal mechanism accounting for inspiratory aerodynamic valving in the avian lung.     

Best evidence in critical care medicine Selective digestive decontamination decreases mortality and morbidity in the intensive care

SDD reduces ICU and in-hospital mortality, the length-of-stay in the ICU, the frequency of colonization with resistant GNB, and the total costs of antibiotic treatment. This supports the use of SDD in all patients expected to be on mechanical ventilation for at least two days in ICUs that have low prevalence of VRE and MRSA.     

结肠回肠反流与回肠黏膜结肠化相关性的实验研究

目的探讨结肠回肠反流后回肠末端黏膜结肠化的机制.方法取SD大鼠60只,均为雄性,体重25¨3∞g,随机分为实验组和对照组,分别进行末端回肠-盲肠侧侧吻合术或回肠末端手术缝线,2个月后处死动物并取组织进行观察.结果实验组术后一般状况良好.大体形态学观察:实验组回肠末端黏膜表现为绒毛萎缩、间距增宽、沟变浅、光滑性增强.病理组织学:实验组表现为黏膜绒毛萎缩、间距增宽、沟变浅、上皮细胞变短、杯状细胞增多.电镜观察:实验组可见绒毛变小、变短或脱落;微绒毛变短、分布不均匀;杯状细胞数目在非坏死区增多.结论结肠-回肠反流后可导致回肠末端黏膜结肠化的变化,它可能是慢性末端回肠炎的发病基础或前期表现.     

人源化抗体构建过程中假链的产生及应对策略

目的在人源化抗体构建过程中，采用方便、快捷的分子克隆手段。消除SP2／0内源性畸形轻链转录本以获得正确的轻链cDNA。方法在mRNA抽提时，不用常规的TRIZOL法抽提总RNA，而采用经腹腔培养。生长状态良好的杂交瘤细胞。用QIAGEN公司Oligotex Direct mRNA Purification Kit，将polyA^＋的mRNA富集。可有效减少畸变转录本的含量，提高功能型mRNA的丰度。利用polyA^＋RNA。采用RT-PCR，我们成功地克隆到了轻链可变区序列，序列分析证实读码框完全正确，属于轻链可变区基因。结果NCBI数据库BLAST显示。克隆的基因序列符合小鼠lg可变区特征，具有正确的CDR和FR功能区及VJ连接区。结论采用polyA^＋ mRNA富集技术，成功克隆获得阻断型抗人CD154 mAb（4F1）单克隆抗体的轻链、重链可变区基因，成功地消除了SP2／0内源性畸形转录本对免疫球蛋白功能性轻链基因的影响。     

麻痹性痴呆12例临床分析

目的探讨麻痹性痴呆(GPI)患者的临床表现,实验室检查、影像学、脑电图特征以及诊断、治疗及预后。方法回顾性分析经临床和实验室确诊的12例GPI患者的相关资料。结果GPI患者临床以智能障碍、精神异常、癫痫最常见。12例患者血清甲苯胺红凝集试验(TRUST)和梅毒螺旋体明胶凝集试验(TPPA)均( ),脑脊液TPPA均( ),而TRUST( )9例。头颅MRI检查结果示大脑皮质萎缩。3例以肢体抽搐为表现者脑电图可见广泛中高幅尖慢波,余脑电图为弥漫性慢波。经抗梅毒治疗,痊愈4例,显效5例,好转3例。结论GPI现已是我国神经梅毒分型中极常见类型,多见于中年男性,临床表现多变,早期误诊率高,早期发现、及时正规治疗预后好。