Retrograde, trans-synaptic and transneuronal transport of fragment C of tetanus toxin by sympathetic preganglionic neurons

The atoxic binding fragment of tetanus toxin, Fragment C, was injected into paravertebral ganglion 14, the avian homologue of the mammalian stellate ganglion. Postinjection survival intervals were varied from 2.5 h to 33 days. Experiments performed at the shortest survival time of 2.5 h showed that Fragment C was retrogradely transported by sympathetic preganglionic axons at a rate greater than or equal to 10 mm/h. At survival times ranging from 5 to 15 h. Fragment C-positive, retrogradely labeled sympathetic preganglionic neurons were observed within the last cervical spinal segment and throughout the first three thoracic spinal cord segments. Sporadic retrograde labeling of sympathetic preganglionic neurons was evident within the fourth and fifth thoracic spinal cord segments. Fragment C-labeled perikarya and dendrites exhibited both diffuse cytoplasmic immunostaining as well as intracellular, perinuclear accumulations of small. Fragment C-positive granules. Retrogradely labeled preganglionic neurons were found within both autonomic subnuclei within avian thoracic spinal cord; the column of Terni and the nucleus intercalatus spinalis. The distribution and numerical density of retrogradely labeled sympathetic preganglionic neurons indicated further that: (a) both myelinated and unmyelinated preganglionic axons appear to be capable of intra-axonally transporting Fragment C; and (b) it is unlikely that there is differential Fragment C labeling of a morphologically distinct population of sympathetic preganglionic neurons within or across subnuclei. Fragment C is transferred out of sympathetic preganglionic somas and dendrites into the surrounding neuropil at an aggregate rate greater than or equal to 5 mm/h. Trans-synaptic transport was evident at postinjection survival times as short as 5 h and continued to increase in density within the sympathetic preganglionic neuropil for 24 h. Fragment C-positive terminal labeling persisted for at least 20 days. At survival times greater than or equal to 1 day. Fragment C-positive puncta and weak intracellular labeling of neurons were evident in areas of the spinal gray outside of the nuclear boundaries of the column of Terni and nucleus intercalatus. The regions showing evidence of trans-synaptic and transneuronal labeling included: (a) a group of small cells dorsal to the column of Terni, (b) lamina V and (c) lamina VII. This expansion of Fragment C-labeled neuronal elements was segmental in organization and co-extensive with the retrograde labeling pattern of sympathetic preganglionic neurons. Spinal interneurons in these regions may provide segmental, monosynaptic input to sympathetic preganglionic neurons. Fragment C leaked into the systemic circulation from the site of injection in paravertebral ganglion 14.(ABSTRACT TRUNCATED AT 400 WORDS)     

Temporomandibular joint arthrography following surgical treatment of internal derangements

Arthrograms of the temporomandibular joint were obtained in 20 symptomatic joints that had previous reconstructive arthroplasty with disk repositioning because of internal derangements. Preoperative arthrograms were available for comparison in 18 joints. Symptoms resulting in a postoperative arthrogram included pain, limited ability to open the mouth, and clicking of the joints. Postoperative arthrographic findings included limited anterior translation of the condyle (90%), irregularity in outline of the intraarticular contrast agent (60%), a conical configuration of the posterior recess (25%), decreased size of the joint (28%), anterior displacement of the meniscus (25%), and perforated meniscus (15%). Many of these findings may have resulted from fibrosis and scarring, which may be a response to intraarticular bleeding. The mechanism by which the fibrosis causes the postsurgical arthrographic features is discussed.     

Quality of life (QOL) assessment of MIP (mitomycin, ifosfamide and cisplatin) chemotherapy in advanced non-small cell lung cancers (NSCLC)

BACKGROUND: Quality of life (QOL) assessment has emerged to measure and quantify the balance between treatment benefit and toxicity, and has a value in predicting response and overall survival in cancer patients. METHODS: From July 1995 to February 1997, 38 symptomatic patients with advanced non-small cell lung cancer (NSCLC) were treated with MIP chemotherapy (mitomycin 6 mg/m2, ifosfamide 3000 mg/m2 and cisplatin 50 mg/m2 on day 1 every 3 weeks). Patients were assessed for QOL including physical well-being, general symptoms and lung cancer-specific symptoms, as well as objective response. RESULTS: The overall response rate was 38.9% (14/36, all were partial response) and the median duration of response was 3.5 months [95% confidence interval (CI) 2.0-4.0]. The median duration of overall survival was 7 months (95% CI 5.9-8.5). The overall improvement of QOL was 58.3% with 21 patients feeling better on treatment. The toxicity of chemotherapy was mild, mainly nausea/vomiting and minimal alopecia. Using multiple clinical predictors of survival (age, histology, stage, performance status), only change of QOL emerged significantly (P = 0.0007). CONCLUSIONS: MIP had an endurable response and low toxicity profile, and provided good QOL. Integral QOL data in our study provided the strong prediction of survival in advanced NSCLC. Further experienced QOL study will provide greatly enhanced outcome data in clinical trials.      

金翼黄芪甙A的化学结构和绵毛黄芪甙ⅩⅤ及7,2′-二羟基-3′,4′二甲氧基异黄烷-7-O-β-D-葡萄糖甙二维核磁共振谱的研究

从金翼黄芪中分离出金翼黄芪甙A(Ⅰ),绵毛黄芪甙XV (Ⅱ),7,2′-二羟基-3′,4′-二甲氧基异黄烷-7-O-β-D-葡萄糖甙(Ⅲ),大豆皂甙Ⅰ,胡萝卜甙及β-谷甾醇。Ⅰ为新化合物,确定其结构为3-O-[α[-L-鼠李吡喃糖基(1→2)-D-木吡喃糖基]-环黄芪醇。并应用二维核磁共振相关谱对Ⅱ和Ⅲ的~1H和~(13)C化学位移信号进行了全面归属。     

Ferrous fumarate deteriorated plasma antioxidant status in patients with Crohn disease

BACKGROUND: Iron deficiency anaemia is a frequent complication of Crohn disease. Treatment with ferrous iron (Fe2-) compounds is often unsatisfactory and is associated with gastrointestinal side effects. Theoretically, oral iron supplementation may even be harmful, because iron may reinforce intestinal inflammation by catalysing production of reactive oxygen species. We investigated the effect of ferrous iron on disease activity and plasma antioxidant status in patients with active Crohn disease. METHODS: Ten patients with Crohn disease and iron deficiency and 10 healthy controls were given ferrous fumarate 120 mg for 7 days. The Crohn Disease Activity Index, gastrointestinal complaints and blood samples for antioxidant status, anaemia, inflammation and iron absorption were investigated on day 1 and day 8. RESULTS: During 1 week of ferrous fumarate supplementation, the Crohn Disease Activity Index tended to increase (P = 0.071). Patients experienced aggravation of diarrhoea, abdominal pain and nausea. Plasma-reduced cysteine was lower (P = 0.038) in patients than it was in controls. One week of ferrous iron supplementation further decreased reduced cysteine (P < 0.001) and significantly decreased plasma-reduced glutathione (P = 0.004) in the patients. Serum iron increased significantly in patients after an oral iron load test (from 5.8 +/- 3.2 micromol/L to 30.9 +/- 13.1 micromol/L). CONCLUSIONS: Treatment of iron deficiency with ferrous fumarate deteriorated plasma antioxidant status and increased specific clinical symptoms in patients with active Crohn disease. Plasma reduced cysteine may be a sensitive indicator for oxidative stress in the intestine.     

Acute toxicity and first clinical results of intensive postinduction therapy using a modified busulfan and cyclophosphamide regimen with autologous bone marrow rescue in first remission of acute myeloid leukemia [see comments]

The combination of high-dose busulfan (16 mg/kg) and 200 mg/kg cyclophosphamide is gaining increasing significance as a preparative regimen prior to autologous, syngeneic, or allogeneic marrow transplantation. A new regimen of high-dose busulfan in conjunction with a reduced dose of 120 mg/kg cyclophosphamide has recently been described as a preparative regimen prior to allogeneic transplantation. To determine the drug-related nonhematologic toxic effects of this new regimen without confounding factors associated with allogeneic transplantation, we conducted a pilot study using this new regimen in 20 patients with acute myeloid leukemia (AML) in first remission prior to autologous unpurged marrow transplantation. All patients experienced transient non-life-threatening acute drug-related toxicity with skin reactions in 20 (100%), nausea and vomiting in 20 (100%), oral mucositis in 18 (90%), hepatic functional impairment in 17 (85%), hemorrhagic cystitis in three (15%), and generalized seizures in two (10%) of these patients, respectively. Two procedural, fatal complications resulted from infectious causes that were not directly related to the speed of hematopoietic reconstitution or the toxicity of the preparative regimen. The 3-year event-free survival estimate (55% +/- 11%) and probability of leukemic recurrence (38% +/- 11%) attained with this new regimen in recipients of autografts in first remission of AML are promising and challenge comparisons with preparative regimens employing combinations of cytotoxic agents or total body irradiation (TBI).