Scintigraphic visualization of intrathecal liposome biodistribution

Background: Liposomes containing local anaesthetics have been administered intrathecally and in the epidural space. Poor attention has been given to the pharmacokinetics of liposomes as drug carriers. Therefore, we observed the biodistribution of liposomes after intrathecal injection in rats by scintigraphic imaging during 24 h.
Methods: We administered ⁹⁹Tc-labeled multilamellar (MLV) and small unilamellar vesicles (SUV) of defined size and volume dispersities into the cerebrospinal fluid at the lumbar level. Those vesicles were free of contamination by radiolabeled colloids as visualized by light and electron microscopy and of neurotoxic products from phosphatidylcholine hydrolysis and peroxidation, both during the preparation process and after 24 h incubation in cerebrospinal fluid at 37°C in vitro.
Results: SUV immediately diffused from the lumbar site of injection to the head and were cleared between 1 and 24 h after injection. MLV were cleared more slowly from the spinal space and appeared in the head region 1 h after injection where they accumulated up to 24 h. These differences were explained in terms of vesicle sizes and volumes. SUV with 0.05 μm diameters were rapidly absorbed into the blood through the arachnoid granulations. In contrast, particles larger than the upper size limit of the arachnoid granulations permeability (±8 μm) could accumulate in the head with a slow elimination rate.
Conclusion: This difference in clearance from the intrathecal space outlines the importance of defining the size of the liposomes, the distribution of a tracer or a drug inside the liposomal preparation, the chemical stability and the absence of toxic degradation products of liposome formulations before clinical use.     

脊髓萎缩（附2例报告）

本文报告了两例脊髓萎缩，并结合文献复习讨论了该病的好发部位、病因、临床表现、诊断和治疗。脊髓萎缩的病因多为继发性，也可为特发性。根据临床表现结合脊髓ＣＴ造影及ＭＲＩ检查，可以明确诊断。     

Bone mineral status in paraplegic patients who do or do not perform standing

Bone mineral density (BMD) was assessed by dual-photon X-ray absorptiometry at the lumbar spine (L3, L4), the proximal femur and the femoral shaft, and by single-photon absorptiometry at the forearm in 53 patients with complete traumatic paraplegia of at least 1 year's duration and in age- and sex-matched healthy controls. The patients did (n=38) or did not (n=15) regularly perform passive weightbearing standing with the aid of a standing device. Compared with the controls, the BMD of paraplegic patients was preserved in the lumbar spine and was markedly decreased in the proximal femur (33%) and the femoral shaft (25%). When considering all patients performing standing, they had a better-preserved BMD at the femoral shaft (p=0.009), but not at the proximal femur, than patients not performing standing. BMD at the lumbar spine (L3,L4) was marginally higher in the standing group (significant only for L3;p=0.040). A subgroup of patients performing standing with use of long leg braces had a significantly higher BMD at the proximal femur than patients using a standing frame or a standing wheelchair (p=0.030). The present results suggest that passive mechanical loading can have a beneficial effect on the preservation of bone mass in osteoporosis found in paraplegics.     

Differential effects of substance P on serotonin-modulated spinal nociceptive reflexes

Recent immunohistochemical studies indicate the presence of a bulbospinal substance P (SP) system, as well as a bulbospinal serotonin (5-HT) system, involved in spinal pain transmission. Although electrophysiological studies indicate that SP may modulate the effects of 5-HT on post-synaptic spinal nociceptive neurons, the functional relationship between SP and 5-HT on “pain behavior” remains obscure. To bridge this gap between mechanism and behavior, the purpose of the present study was to determine specific postsynaptic behavioral effects of SP and 5-HT on local spinal nociceptive reflexes in spinally transected animals. Administration of the 5-HT agonists 5-methoxydi-methyltryptamine (5-MeODMT) (0, 0.5, 1.5, 2.0 mg/kg) and quipazine (0, 5, 10, 20 mg/kg) 2 days after transection significantly expanded the receptive field (RF) areas of three spinal reflexes, as previously reported. Intrathecal administration of SP alone (0, 0.25, 2.5, 7.5 ng) also resulted in hyperalgesia, indicated by a significant expansion of the RF areas of all three nociceptive reflexes. However, administration of SP, in animals pretreated with 5-HT agonists, decreased the 5-HT-induced expansion of RF size. Therefore, SP had opposite effects on spinal nociceptive reflexes depending on whether or not the animal was pretreated with 5-HT agonists, i.e., hyperalgesia in the absence of 5-HT agonists, and analgesia in the presence of 5-HT agonists. The two effects of SP on local spinal reflexes may be related to the anatomical organization of the two spinal SP systems: 1) SP released from primary afferents facilitates nociceptive reflexes, and 2) SP associated with the descending bulbospinal system interacts with the descending bulbospinal 5-HT system and inhibits nociceptive reflexes. The present results help explain contradictory literature regarding the effect of SP on spinal nociceptive reflexes.     

尼卡地平控制性降压对家犬脊髓血流的影响

目的　观察尼卡地平控制性降压对家犬脊髓血流的影响。方法　成年杂种犬 6只 ,体重 12 5～ 16kg ,以 2 5 %硫喷妥钠麻醉。股动脉置管监测MAP。以尼卡地平 8μg·kg 1·min 1持续静脉注射控制性降压。以激光多普勒血流仪测定脊髓血流 (SCBF)。结果　降压前MAP为 (12 5 7±10 6 )mmHg ,降压后为 (72 0± 11 2 )mmHg ,平均下降 4 2 8%。降压前SCBF为 (9 80± 1 0 5 )v ,降压后为 (8 0 4± 0 96 )v ,降低幅度为 18%。结论　尼卡地平控制性降压对SCBF影响较小 ,可安全用于脊髓手术。     

腰麻辅助硬膜外麻醉在全子宫切除术中的应用分析

目的:观察腰麻辅助硬膜外麻醉在全子宫切除术中的应用效果。方法:选择328例全子宫切除术病人,随机分为试验组(143例)、对照组(185例),均取L_(1-2)棘突间隙行硬膜外腔穿刺置管,对照组常规用药,试验组另取L_(3-4)棘突间隙行腰麻,观察各组的麻醉效果,术中探查牵拉子宫时病人的反应,血压及心率的变化。结果:试验组的麻醉良好率、肌松情况优于对照组(P<0.01),骶神经阻滞情况试验组完全阻滞,而对照组出现骶神经阻滞不全,首次剂量试验组少于对照组(P<0.01)。牵拉子宫后各组病人血压、心率均较牵拉前下降,且与牵拉前比较有显著差异(P<0.05)。结论:在全子宫切除术中应用腰麻辅助硬膜外麻醉优于单纯硬膜外麻醉,有一定临床应用意义。     

Cystic spinal dysraphism of the cervical and upper thoracic region

Background Cystic dysraphic lesions of the cervical and upper thoracic region are rare and only a few series have been published about the topic. These malformations can be divided into categories that include both myelocystoceles and the so-called cervical meningoceles or myelomeningoceles.Methods A retrospective study of 18 patients was conducted.Results In 17 patients a squamous or a cicatricial epithelium of variable thickness covered the dome of the lesions, while the base was covered with full-thickness skin. In one case the skin was entirely normal. Four patients displayed associated CNS malformations and three more had systemic congenital anomalies. All patients underwent surgical exploration and the length of time between birth and surgery ranged from 6 h to 9 months. The most frequent surgical finding, seen in 14 patients, was a stalk connecting the dorsal surface of the spinal cord to the cyst. In three patients the findings were consistent with myelocystocele. Only in one case was a true meningocele found. Hydrocephalus and Chiari II malformation were not as consistently associated as in myelomeningoceles. Neurological signs and symptoms were not so marked as in myelomeningoceles and were found in the follow-up of four patients. In two of them there was a non-progressive deficit, probably expressing an imperceptible involvement of the nervous system in the first year of life. The histopathological findings were of three types: neuroglial stalks, fibrovascular stalks and myelocystoceles.Conclusions Cystic dysraphisms of the cervical and upper thoracic region differ clinically and structurally from meningomyelocele and have a more favorable outcome. We believe that these malformations have not been properly labeled and propose a classification based on the structures found inside the cyst.     

Anal Canal Cancer

PURPOSE: This study was designed to obtain an updated population-based perspective on anal canal cancer incidence rates, demographics, and outcomes using a nationwide database. Eight-five percent of all carcinomas of the anus are anal canal cancers, and previous studies suggest that incidence rates may be rising. Although the most successful treatment for anal canal cancer has been chemoradiation, little information at the population-level exists regarding demographics, treatment, and survival. METHODS: All patients diagnosed with anal canal cancer from 1973 to 1998 in the Surveillance Epidemiology and End Results cancer registry were analyzed. Data regarding demographics, cancer characteristics, treatment, and survival were assessed. Univariate and multivariate survival analyses were performed. RESULTS: A total of 4,841 patients were studied (mean age was 61 years; 62 percent female). Female patients were significantly older than male patients (65 vs. 58 years; P < 0.0001). There was a yearly increase in incidence of anal canal cancers (from 1973–1998). Disease prevalence by stage was localized (53 percent), regional (38 percent), and distant (9 percent). Racial/stage differences were seen, because black patients had less localized disease than white patients (46 vs. 53 percent; P < 0.01). Overall five-year survival for the entire cohort was 53 percent, and cancer-specific survival was 84 percent. Survival improved per decade (based on year of diagnosis). Significant survival differences in race were noted, but were less when the receipt of treatment was considered. CONCLUSION: Although most anal canal cancer reviews are single institutional series, this study was performed with population-based data. The incidence of anal canal cancer is increasing, and overall survival rates are improving. Important disparities in care were identified, which need to be addressed.     

Illness-induced hyperalgesia is mediated by spinal neuropeptides and excitatory amino acids

The spinal cord dorsal horn contains neural mechanisms which can greatly facilitate pain. We have recently shown that ‘illness’-inducing agents, such as intraperitoneally administered lipopolysaccharide (LPS; bacterial endotoxin), can produce prolonged hyperalgesia. This hyperalgesic state is mediated at the level of the spinal cord via activation of the NMDA-nitric oxide cascade. However, prolonged neuronal depolarization is required before such a cascade can occur. The present series of experiments were aimed at identifying spinal neurotransmitters which might be responsible for creating such a depolarized state. These studies show that LPS hyperalgesia is mediated at the level of the spinal cord by substance P, cholecystokinin and excitatory amino acids acting at non-NMDA sites. No apparent role for serotonin or kappa opiate receptors was found.     

牙髓根管感染厌氧菌培养结果分析

从３４例牙髓根管感染中共分离出厌氧菌１１８株，经菌属分类依次为消化链球菌属，拟杆菌属，梭杆菌属，放线菌属，韦荣氏球菌属和珠网菌属，其中前３属为７７株，分离率为６５．３％，这一结果显示该３属细菌与极管感染有密切关系，是牙髓根管感染的优势菌。