6-(4-酰基-1-哌嗪乙酰氨基)-3,4-二氢-2(1H)-喹啉酮类化合物的合成及正肌力活性初探

目的 :寻找具有正性肌力活性的化合物。方法 :根据文献报道的二氢喹啉酮类正性肌力药物的结构特点 ,设计、合成了其类似物。以苯胺为起始原料经多步合成 ,对所得化合物用离体豚鼠心脏与主动脉观察了心肌收缩力、扩血管作用及心率。结果 :合成了 1 0个 6 ( 4 酰基 1 哌嗪乙酰氨基 ) 3 ,4 二氢 2 ( 1H) 喹啉酮类化合物 ( 4a～ 4j) ,均为未见文献报道的化合物。结论 :初步药理试验表明 ,化合物 ( 4h)显示了正性肌力及扩血管活性。     

Inflammatory bowel disease and predisposition to osteopenia

The prevalence of osteopenia in children with inflammatory bowel disease (IBD) is unknown. The effect of nutritional state, disease activity, and steroid therapy on bone mineral content (BMC) of whole body, lumbar spine, and left femoral neck measured by dual energy x ray absorptiometry in 32 children with IBD was assessed by comparison with 58 healthy local school children. Using the control data, a predicted BMC was calculated taking into account bone area, age, height, weight, and pubertal stage. The measured BMC in children with IBD was expressed as a percentage of this predicted value (% BMC). Mean (SD) % BMC was significantly reduced for the whole body and left femoral neck in the children with IBD (97.0 (4.5)% and 93.1 (12.0)% respectively, p < 0.05). Of the children with IBD, 41% had a % BMC less than 1 SD below the mean for the whole body and 47% at the femoral neck. Reduction in % BMC was associated with steroid usage but not with the magnitude of steroid dose, disease activity, or biochemical markers of bone metabolism. In conclusion, osteopenia is relatively common in childhood IBD and may be partly related to the previous use of steroids.     

The low dose ACTH stimulation test is less sensitive than the overnight metyrapone test for the diagnosis of secondary hypoadrenalism

OBJECTIVE: The 1 microgram ACTH stimulation test has been advocated as a sensitive indicator of the integrity of the hypothalamic-pituitary-adrenal axis in patients with suspected hypopituitarism. The aim of our study was to define the normal response to 1 microgram ACTH stimulation in a control population and to study the sensitivity and specificity of the test in a group of patients with suspected pituitary disease. DESIGN: A prospective analysis of the performance of the 1 microgram ACTH stimulation test in a group of patients with pituitary disease. PATIENTS: The cortisol response to 1 microgram ACTH was evaluated in 21 normal subjects and 65 patients with pituitary disease. The patients with pituitary disease were divided into two groups according to the 11-deoxycortisol response to overnight metyrapone: normal (11-deoxycortisol > 200 nmol/l) and subnormal ACTH secretory status (11-deoxycortisol < 200 nmol/l). MEASUREMENTS: In both controls and patients, blood was sampled for cortisol at - 15, 0, + 20, + 30, + 40 and + 60 minutes after intravenous administration of 1 microgram synthetic ACTH (Synacthen(R)). The overnight metyrapone test was performed only in the subjects with pituitary disease. Metyrapone (30 mg/kg) was administered orally at 2300 h and blood was sampled at 0830 h the following morning for 11-deoxycortisol. RESULTS: The 65 patients with pituitary disease were categorized according to the 11-deoxycortisol response to metyrapone as follows: 53 normal (11-deoxycortisol > 200 nmol/l) and 12 subnormal (< 200 nmol/l). The 12 patients who failed the metyrapone test had a significantly impaired cortisol response to low dose ACTH stimulation at all time points when compared with both the control group and the pituitary patients with a normal response to metyrapone (P < 0.001). Comparing the pituitary patients who had a normal response to metyrapone and the control subjects, there was no significant difference in the cortisol response to ACTH (P > 0.05). The minimum cortisol response at 30 minutes in the 21 control subjects was 414 nmol/l and this was defined as the minimum normal cortisol response to 1 microg ACTH. Using this criterion, six of the 12 patients with a subnormal response to metyrapone had a normal cortisol response to low dose ACTH stimulation. Empirically increasing the cortisol cut-off to 600 nmol/l increased the sensitivity of the low dose ACTH test to 83%, although the specificity was reduced from 100% to only 58%. CONCLUSIONS: The normal cortisol response to low dose ACTH stimulation in 50% of the patients with ACTH deficiency proven on metyrapone testing suggests that the 1 microgram ACTH stimulation test, like the 250 microgram-test, lacks sensitivity for the diagnosis of ACTH deficiency.     

Isolation and characterization of a spontaneously immortalized human breast epithelial cell line, MCF-10

Two sublines of a breast epithelial cell culture, MCF-10, derived from human fibrocystic mammary tissue exhibit immortality after extended cultivation in low calcium concentrations (0.03-0.06 mM) and floating transfers in low calcium (MCF-10F), or by trypsin-Versene passages in the customary (normal) calcium levels, 1.05 mM (MCF-10A). Both sublines have been maintained as separate entities after 2.3 years (849 days) in vitro and at present have been in culture for longer than 4 years. MCF-10 has the characteristics of normal breast epithelium by the following criteria: (a) lack of tumorigenicity in nude mice; (b) three-dimensional growth in collagen; (c) growth in culture that is controlled by hormones and growth factors; (d) lack of anchorage-independent growth; and (e) dome formation in confluent cultures. Cytogenetic analysis prior to immortalization showed normal diploid cells; although later passages showed minimal rearrangement and near-diploidy, the immortal cells were not karyotypically normal. The emergence of an immortal culture in normal calcium media was not an inherent characteristic of the original tissue from which MCF-10 was derived since reactivated cryo-preserved cells from cultures grown for 0.3 and 1.2 years in low calcium were incapable of sustained growth in normal calcium.     

Localized orbital rhabdomyosarcoma. An interim report of the Intergroup Rhabdomyosarcoma Study Committee

Children with rhabdomyosarcoma (RMS) (1461 total cases) were included in two prospective, randomized protocols conducted by the Intergroup Rhabdomyosarcoma Study (IRS) Committee from November 1972 to June 1983. Treatment assignment was determined by extent of tumor at diagnosis (clinicopathologic group) and not by primary site. Accordingly, 127 patients with RMS confined to the region of the eyelid and orbit were treated by a variety of regimens characterized by initial partial tumor resection followed by concurrent multiagent chemotherapy and orbital radiation therapy. Recurrent tumor developed in ten patients. Seven relapsed initially in the orbit (of whom 4 were salvaged) and three in regional nodes. In addition to the six patients who died of tumor, three died of other causes for a 93% 3-year actuarial survival rate. In 89 children who had subtotal resection or biopsy only, the local control rate with radiotherapy and chemotherapy was 94%.     

ACQUIRED PHARYNGEAL DIVERTICULUM FOLLOWING ANTERIOR CERVICAL FUSION OPERATION

SUMMARY We report an unusual case of a pharyngeal diverticulum arising as a result of extrusion of a bone graft inserted during anterior cervical fusion operation. The dense scar tissue at the site of extrusion of the bone graft probably caused traction on the posterior pharyngeal wall, with the development of a pharyngeal pouch. This is believed to be the first case with acquired pharyngeal diverticulum following anterior cervical fusion to be recorded in the literature.     

汉语阅读障碍儿童在本顿视觉保持测验中的反应特征

目的:比较阅读障碍儿童与正常儿童在本顿视觉保持测验中的反应特征,探索阅读障碍儿童视觉空间记忆能力的特点。方法:①2005-07/2006-05在儿童发育行为门诊遴选阅读障碍儿童20名(平均年龄10.2岁),按1∶1配对原则,选择年龄、性别、年级和家庭状况等条件与阅读障碍组相似的20名正常阅读能力儿童为对照组(平均年龄10.1岁)。②应用国内修订版本顿视觉保持测验C式B法,D式C法和E式D法对两组儿童进行个别测试。C式图卡呈现5s后让被试默画(视觉记忆能力),D式图卡让被试临摹(视觉结构能力),E式图卡呈现10s后间隔15s再让被试默画(视觉延迟记忆能力)。③对两组儿童的视觉记忆保持能力、视觉结构能力和延迟记忆能力进行测试,分别记录两组儿童测验的正确分(每一图卡根据全或无的原则记1或0分,总分0～10)及错误次数(错误类型分为遗漏或增加、变形、持续、旋转、位置错误和大小错误6个范畴),进行配对t检验。结果:40名受试者均进入结果分析。①正确得分:在视觉记忆和视觉结构能力测验中阅读障碍组低于对照组(5.00±2.45,6.60±1.82,P=0.019;7.50±2.44,8.95±1.32,P=0.015),在视觉延迟记忆测试中,两组得分比较差异不显著(P=0.077)。②总错误分:在视觉记忆和视觉结构能力测验中阅读障碍组高于对照组(7.65±4.20,4.90±3.24,P=0.016;3.20±3.93,1.15±1.46,P=0.035),在视觉延迟记忆测试中,两组得分比较差异不显著(P=0.389)。③错误类型:阅读障碍组儿童在视觉记忆能力测试中变形和持续性错误次数均显著多于对照组(3.95±2.40,1.75±1.52;0.35±0.67,0;P均<0.05),在视觉结构能力测试中变形错误次数显著多于对照组(1.35±1.69,0.35±0.75,P<0.05)。结论:阅读障碍儿童的视觉空间短时记忆能力、视觉结构和视觉运动整合能力存在缺陷。     

Screening for ‘window‐period’ acute HIV infection among pregnant women in rural South Africa

Objectives

The aim of this study was to evaluate the HIV‐1 RNA pooled nucleic acid amplification testing (NAAT) strategy to screen pregnant women in the ‘window period’ of acute HIV infection (AHI) in rural South Africa.

Methods

In 2007 and 2008, 750 consecutive pregnant women on their first antenatal care visit to a primary health care clinic were tested anonymously for HIV infection. HIV‐1 RNA pooled NAAT was performed on HIV antibody‐negative samples. All positive pools were tested individually and positive samples were classified as incident cases to calculate HIV incidence.

Results

The overall HIV prevalence was 37.3% [95% confidence interval (CI) 34.3–41.3]. Of the 467 HIV antibody‐negative samples, four (0.9%) were HIV‐1 RNA‐positive. The mean viral load in the four samples was 386 260 HIV‐1 RNA copies/mL (range 64 200–1 228 130). The HIV incidence was 11.2% per year (95% CI 0.3–22.1) and all women with AHI were ≤21 years of age.

Conclusions

Identifying AHI in pregnancy is important for health interventions to reduce perinatal and heterosexual transmission of HIV, and to estimate HIV incidence for epidemiological surveillance.