Oestrogen‐Independent Circadian Clock Gene Expression in the Anteroventral Periventricular Nucleus in Female Rats: Possible Role as an Integrator for Circadian and Ovarian Signals Timing the Luteinising Hormone Surge

Periodic ovulation in rats, mice and hamsters is the result of a surge in luteinising hormone (LH) that depends on circadian gating signals emerging from the master circadian clock within the suprachiasmatic nucleus (SCN) and rising ovarian oestrogen levels. These two signals converge into the anteroventral periventricular nucleus (AVPV) and lead to the release of kisspeptin, which is responsible for surges of gonadotrophin‐releasing hormone and, in turn, of LH release. How the AVPV integrates circadian and reproductive signals remains unclear. In the present study, we show that the female rat AVPV itself shows circadian oscillations in the expression of the clock genes PER1 and BMAL1, which lie at the core circadian clockwork of mammals. In ovariectomised females treated with oestradiol (E₂), these oscillations are in synchrony with the AVPV rhythmic expression of the KISS1 gene and the gene that codes for the arginine‐vasopressin (AVP) receptor AVPr1a. Although clock gene oscillations are independent of oestrogen levels, circadian expression of Kiss1 and Avpr1a (also referred to as V1a) mRNA is blunted and absent, respectively, in ovariectomised animals without E₂ replacement. Because AVP is considered to be a critical SCN transmitter to gate the LH surge, our data suggest that there is a circadian oscillator located in the AVPV, and that such a putative oscillator could, in an oestrogen‐dependent manner, time the sensitivity to circadian signals emerging from the SCN and the release of kisspeptin.     

Gamma-interferon in aplastic anemia: inability to detect significant levels in sera or demonstrate hematopoietic suppressing activity

A radioimmunoassay (RIA) was used to quantitate biologically active gamma interferon (INF-gamma) in sera and in supernatants of cultured mononuclear cells obtained from 50 patients with aplastic anemia. Only five of the 50 serum samples had INF-gamma levels above background (greater than 0 less than 0.5 units per mL). Detectable levels of spontaneous INF-gamma (0.3 to 868 U/mL) were found in 18 of the 50 mononuclear cell supernatants tested. The addition of patient sera or INF-gamma positive supernatants to cultures of normal hematopoietic colonies did not result in reduced colony growth. Flow cytofluorimetric analysis of mononuclear cells failed to establish a correlation between the presence of INF-gamma in supernatants and the number of activated T cells or natural killer (NK) cells in the mononuclear cell population. However, a significant correlation did exist between the presence of monocytes and the production of INF-gamma. Contrary to previous reports, our data suggest that patients with aplastic anemia do not have high circulating levels of INF-gamma. Unstimulated mononuclear cells from some patients will produce significant levels of INF-gamma, but this does not result in decreased in vitro hematopoiesis.     

Acquired malposition of the colon and gallbladder in patients with cirrhosis: CT findings and clinical implications

Topographic relationships among the gallbladder, liver, hepatic flexure of the colon, right hemidiaphragm, and anterolateral peritoneal reflection were evaluated with computed tomography in 75 patients with biopsy-proved cirrhosis and in 200 control subjects to determine the effect of cirrhotic liver morphology on the anatomy of the right upper quadrant of the abdomen. Interposition of the colon between the liver and anterolateral abdominal wall and/or diaphragm was seen in 18 of the 75 (24%) cirrhotic patients and in six of the 200 (3%) control subjects. There was a strong correlation among gallbladder malposition, colonic interposition, and a ratio of transverse caudate lobe width to right lobe width (C/RL) exceeding 0.60. Patients with cirrhosis, colonic interposition, and gallbladder malposition had a mean C/RL of 0.62, compared with a mean of 0.50 for cirrhotic patients without interposition (P less than .0001). The mean C/RL for control subjects without interposition was 0.43, as compared with 0.69 for control subjects with interposition (P less than .01). These acquired malpositions of the colon and gallbladder may pose a diagnostic dilemma and increase the risk of inadvertent injury during percutaneous liver biopsy, interventional biliary tract procedures, and laparotomy.     

Percutaneous transluminal renal angioplasty: initial and long-term results

Renal artery stenosis in 201 patients with hypertension was treated with percutaneous transluminal renal angioplasty (PTRA). A total of 213 procedures were performed as treatment of 262 separate stenosis. The stenosis was caused by atherosclerosis in 134 cases and by fibromuscular dysplasia (FMD) in 52 cases; the cause was indeterminate in 27 cases. Of the 213 procedures, 172 were successful or resulted in improvement, for a technical success rate of 80.8%. The initial clinical results could be evaluated in 210 cases; cure or improvement was achieved in 80%. There were 23 cases in which neither technical nor clinical success was achieved. Data on the remaining 187 cases were the basis of this long-term follow-up study. The cumulative patency rate at 5 years was 80% in the atherosclerosis group, 89% in the FMD group, and 74% in the indeterminate group. The mortality was less than 1%. Because spasm occurred in 33 cases, causing an infarction in ten instances, antispasmodic medication seems warranted. These long-term results indicate that PTRA is the treatment of choice in patients with renovascular hypertension.     

Normal instability of the hip in the neonate: US standards

In recent years, the use of real-time ultrasonography (US) has enabled dynamic evaluation of the infant hip through a range of motion and stress. Preliminary experience has suggested that a certain amount of instability in the hips of newborns is normal, but no standards have been established. In this study, a group of term neonates whose physical examinations were normal were examined with US on the 1st and 2d days of life. Each hip was imaged in the transverse plane in nonstressed and stressed positions, and movement of the femoral head under stress was quantitated. This displacement under stress was used to establish a normal range of hip instability in neonates. Patterns of hip laxity in boys and girls are identical, and in most infants hip instability diminishes between the 1st and 2d days of life. Our method of quantitating hip instability produces consistent results, with intraobserver 95% confidence intervals of +/- 1.2 mm for each measurement.     

兔膝关节软骨表面形态在短时非周期大强度运动训练后的变化

目的:观察正常软骨表面的形态结构以及短时非周期大强度运动训练对关节软骨的影响。方法:实验于2001-01/09在四川省骨科医院完成。①实验动物:10～12个月龄日本大耳白兔8只,雌雄各半,体质量(3.5±0.2)kg。②实验分组:将动物分为对照组2只,训练组6只,其中训练1,2,3周各2只。③实验干预:训练组兔在电刺激笼中进行训练,训练量为20s刺激1次,刺激时间为0.2～0.5s,动物受刺激后沿刺激笼跑跳数步并转弯。训练120min/d,每组训练60min后休息20min,训练6d/周,星期日休息,分别训练1,2,3周。对照组不放在电刺激笼中,也不进行训练。④实验评估:扫描电子显微镜下观察训练前后兔股骨和胫骨髁软骨表面形态结构的变化;MIAS99图形处理软件计算浅坑(pits)的直径和面积。结果:8只兔均进入结果分析。①正常兔膝关节软骨的表面形态结构:正常软骨表面低倍镜下显示为均匀排列的浅坑,在高倍镜下呈现一种均匀多孔状结构。②运动训练后软骨表面结构的变化:训练后浅坑形态不规则,边缘粗糙,胶原纤维增粗,孔隙不均匀增大。结论:软骨表面正常的形态结构是浅坑,短时非周期大强度训练,未引起纤维断裂和碎屑,说明不会损伤软骨表面形态结构。     

正常兔膝关节表面结构的扫描电镜观察

目的:扫描电镜观察正常兔膝关节表面的结构,为研究关节软骨表面结构提供正常参照。方法:实验于2001-01/09在四川省骨科医院完成。日本大耳白兔8只,10～12个月龄,雌雄各半,体质量(3.5±0.2)kg。通过扫描电镜对8只实验兔股骨髁、胫骨髁的软骨表面进行观察,其中4个髁用锐器划伤。结果:纳入日本大耳白兔8只,均进入结果分析。每个正常髁的表面都显示有大量的浅坑,有锐器划伤的髁则出现了垄沟及隆突。软骨表面在高倍镜下呈现一种均匀多孔状结构。结论:软骨表面唯一呈现的结构是浅坑,垄沟和隆突可能是标本的采集、制作过程中形成的赝象。     

Intraarterial digital subtraction arteriographic evaluation of extremity tumors: comparison with conventional arteriography

Conventional arteriography and intraarterial digital subtraction arteriography (IADSA) were compared in 36 patients with primary bone or soft-tissue tumors of the extremities. The sensitivity of IADSA was at least equal to conventional arteriography for demonstrating normal or abnormal major arteries and feeding arteries, equal to or superior for depicting tumor stains or draining veins, but slightly inferior for revealing minute tumor vessels. An increase of the matrix size from 256 X 256 to 512 X 512 improved these sensitivities. IADSA with 15% diatrizoate contrast material eliminated the contrast material-induced pain in all patients. With a computer-controlled iris setting, an average of 5 minutes of procedure time and 1.7 R of radiation (0.44 mC kg) per examination could be saved. IADSA reduced the cost of an examination by an average of $67. The results indicate that IADSA was diagnostic in all instances and can replace conventional arteriography for the evaluation of extremity tumors.     

Improved outcome for high-risk acute myeloid leukemia patients using autologous bone marrow transplantation and monoclonal antibody-purged bone marrow

We have conducted a 9-year multicenter trial of autologous bone marrow transplantation (ABMT) for acute myeloid leukemia (AML). Remission BM was purged in vitro using monoclonal antibodies (MoAbs; PM-81, AML-2- 23) and complement targeting myeloid differentiation antigens (CD15, CD14). In 1988, the preparative regimen changed from 60 mg/kg/d cyclophosphamide x 2 and fractionated total body irradiation (TBI) total dose, 1,200 cGy (Cy/fTBI), to 4 mg/kg/d busulfan x 4 and 60 mg/kg/d Cy x 2 (Bu/Cy2). Recent analysis (October 1, 1993) shows that the Bu/Cy2 regimen along with the same MoAb purging method yields an improved outcome. Seven first complete-remission (CR) (CR1), 45 second- or third-CR (CR2/3), and 11 first-relapse (R1) patients were treated with chemotherapy and TBI or chemotherapy alone followed by ABMT with MoAb-purged BM. Median age at ABMT for those patients in CR 2/3 and R1 patients was 36 years. Twenty-nine CR 2/3 and R1 patients were conditioned with Cy/fTBI, and 27 CR2/3 and R1 patients were conditioned with Bu/CY. Using the Kaplan-Meier method, the CY/fTBI, CR2/3, and R1 patients have a 3-year disease-free survival (DFS) of 21%. On the other hand, the Bu/Cy2, CR2/3, and R1 patients have a 3-year DFS of 48%. Nineteen CR2/3 and R1 patients relapsed post-ABMT. On analysis by conditioning regimen, those treated with Cy/fTBI have a 3-year relapse rate (RR) of 58%, whereas the patients conditioned with Bu/Cy2 have a 39% 3-year RR. Long-term DFS can be achieved in about 50% of patients with advanced remissions and relapsed AML using Bu/Cy2 with MoAb-purged BM.