To determine if impaired energy metabolism might contribute to some aspects of Alzheimer disease (AD), including the vulnerability of the CA1 region of the hippocampal formation and the altered cytoskeleton evident in neurofibrillary tangles, we examined the effects of metabolic poisons on neuronal damage and cytoskeletal disruption in the hippocampal formation. Intrahippocampal injection of 3-nitropropionic acid (3-NP) and malonic acid resulted in neuronal death, particularly in CA1. Cytoskeletal disruption included loss of dendritic MAP2, but sparing of axonal τ. MK-801 (a noncompetitive NMDA receptor antagonist) did not atenuate the lesions produced by intrahippocampal injection of malonate. MK-801, however, was effective against intrastriatal malonate. Acute systemic 3-NP resulted in neuronal damage and cytoskeletal disruption in the CA1 region of the hippocampal formation, including an extensive loss of MAP2 immuno-reactivity, but sparing of τ. The neuronal loss in CA1 was delayed as compared to striatum. Chronic intraventricular infusion of 3-NP produced a different pattern of neuronal damage. Loss of τ-1 immuno-reactivity was observed in CA3 and CA1 s. oriens, whereas MAP2 immunostaining was preserved. These results demonstrate that chronic and acute administration of metabolic inhibitors produce distinct patterns of neuronal damage and cytoskeletal disruption. The results further suggest a differential involvement of the NMDA receptor in malonate-induced neuronal damage in striatum as compared to the hippocampus. The pattern of neuronal damage and cytoskeletal disruption observed following acute metabolic impairment resembled some aspects of neurofibrillary pathology in AD, but did not result in τ hyperphosphorylation. 相似文献
Background: There is considerable controversy regarding the role of subarachnoid 5% hyperbaric lidocaine in the syndrome transient radicular irritation (TRI). This randomized, double-blinded, prospective study was designed to determine the incidence of TRI and identify factors possibly contributing to its development.
Methods: One hundred fifty-nine ASA physical status 1 or 2 patients undergoing outpatient knee arthroscopy or unilateral inguinal hernia repair were prospectively randomized to receive spinal anesthesia with 5% hyperbaric lidocaine with epinephrine (60 mg with 0.2 mg epinephrine for arthroscopy or 75 mg with 0.2 mg epinephrine for hernia repair), 2% isobaric lidocaine without epinephrine (60 mg for arthroscopy or 75 mg for hernia repair), or 0.75% hyperbaric bupivacaine without epinephrine (7.5 mg for arthroscopy or 9.0 mg for hernia repair) in a double-blinded fashion. On the 3rd postoperative day, patients were contacted by a blinded investigator and questioned regarding the incidence of postoperative complications including TRI, defined as back pain with radiation down one or both buttocks or legs occurring within 24 h after surgery. Postoperatively, time from injection to block resolution, ambulation, voiding, and ready for discharge were recorded by a postanesthesia care unit nurse blinded to the group assignment.
Results: The incidence of TRI was greater in patients receiving lidocaine than in those receiving bupivacaine (16% vs. 0%; P = 0.003). There was no difference in the incidence of TRI between the patients receiving 59% hyperbaric lidocaine with epinephrine and those receiving 2% isobaric lidocaine without epinephrine (16% vs. 16%; P = 0.98). The incidence of TRI was greater in patients undergoing arthroscopy than in those undergoing hernia repair (13% vs. 5%; P = 0.04). There was no difference in discharge times in patients receiving bupivacaine versus those receiving hyperbaric lidocaine with epinephrine (292 vs. 322 min; P = 0.61). 相似文献
A controlled treatment outcome study was conducted comparing the efficacy of memory remediation treatment with no treatment on traumatic brain-injury patients. The memory remediation treatment consisted of both compensatory and executive training skills and was delivered 6 hours weekly over a 2 1/2-week period. Six subjects in the treatment group and 6 subjects in the control group were matched on WAIS-R FSIQ scores, pre-test memory scores and age. Pre-and post-test measures were obtained for both groups on a paragraph memory task. A significant difference was demonstrated between the treatment and control post-test memory scores. The experimental group significantly improved memory scores beyond that of the control group, suggesting that memory remediation is effective for head-injury patients with memory deficits. Discussion of findings and suggestions for further investigation are presented. 相似文献
1. Fifty-five intact and six baroreceptor denervated and vagotomized cats of either sex were anaesthetized intraperito-neally with urethane (400 mg/kg) and a-chloralose (40 mg/kg). Responses of the systemic arterial pressure (SAP), mean SAP (MSAP) and sympathetic vertebral nerve (VNA) and renal nerve activities (RNA) were recorded. 2. In intact animals, monosodium L-glutamate (Glu, 0.1 mol/L, 50 nL) was microinjected into pressor areas of the locus coeruleus (LC), gigantocellular tegmental field (GTF), rostral ventrolateral medulla (RVLM) and dorsomedial medulla (DM), and the depressor areas of caudal ventrolateral medulla (CVLM). The induced actions were compared before and after microinjection of either glutamate antagonists, glutamate diethylester (GDEE, 0.5 mol/L, 50–100nL), a competitive AMPA receptor blocker, or 2-amino-5-phosphonovaleric acid (D-AP5, 0.025 mol/L, 50–100 nL), a competitive N-methyl-D-aspartate (NMDA) receptor blocker. GDEE completely blocked the increases of SAP and VNA elicited from all pressor areas. D-AP5 only partially blocked the pressor but slightly blocked VNA and RNA responses from LC, GTF and DM, particularly those from RVLM. Neither GDEE nor D-AP5 blocked the depressor responses of SAP and two nerve activities elicited from CVLM. 3. In baroreceptor denervated animals, NMDA (2 mmol/L, 50–100 nL) and AMPA (0.2 mmol/L, 50–100 nL) were micro-injected into the same pressor areas of GTF, RVLM and DM and the depressor area of CVLM responsive to Glu activation (0.1 mol/L, 30 nL). In RVLM, DM and CVLM, the results of either NMDA or AMPA were similar to those induced by Glu. However, in GTF, microinjection of either NMDA or AMPA did not induce similar responses to Glu. This suggests that the nature of GTF may differ from RVLM and DM. 4. The above results suggest that the Glu-induced pressor responses from LC, GTF, DM and especially RVLM, are primarily mediated through AMPA receptors. The Glu-induced depressor responses from CVLM may not be predominantly mediated by either AMPA or NMDA receptors. 5. In both baroreceptor-intact and -denervated cats stimulation of the pressor areas often produced an increase of VNA and a decrease of RNA, while in the depressor CVLM decreased both VNA and RNA. The VNA, but not RNA were positively correlated with the pressor responses, while both VNA and RNA were positively correlated with the depressor responses. This may suggest that neurons of the sympathetic vertebral and renal nerves are topographically organized in the brain. 相似文献
Since bone marrow has been shown to contain osteoprogenitor cells, an experiment was devised to test its effects when injected percutaneously into osteotomies and 2-cm bony defects produced in rabbit radii. The parameters tested included callus volume, breaking load, tensile strength, and cross-sectional area of callus at the fracture or bony defect site. At two weeks postgrafting callus volume was significantly higher (p less than 0.01) in the grafted radii than in the contralateral saline controls. By four weeks all four parameters were significantly greater in the bone marrow grafted radii than in the contralateral saline controls. Serial radiographs and histology confirm this advanced fracture healing in the grafted bones. The earlier and more abundant callus, at the bone marrow grafted sites, was felt to provide earlier and greater stability, resulting in decreased early healing time when contrasted with the saline controls. Similarly, the bony defects that were grafted with bone marrow united by a bony bridge, whereas the saline controls did not. Percutaneous bone marrow grafting is a simple semi-invasive technique that may have potential clinical applications. 相似文献
Proximal femoral focal deficiency, an uncommon congenital anomaly, necessitates early radiologic classification for surgical planning and treatment. Objective radiographic criteria, including femoral length index, acetabular depth index, acetabular angle index, and shape of the proximal femur were determined in 49 patients before cartilaginous ossification of the femoral capital epiphysis; final classification was based on follow-up radiographs or findings at arthrography or surgery. These parameters were analyzed to determine the accuracy and contributions of each in classification. Correct classification into one of three groups was possible in 86% of cases with use of three of the parameters: femoral length index, acetabular depth index, and shape of the proximal femur. The acetabular angle was found to contribute insignificantly to classification. Magnetic resonance imaging, used in only one case, depicted the nonossified cartilaginous femoral capital epiphysis, thus obviating the need for invasive diagnostic procedures and facilitating early classification. 相似文献