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81.
82.
A new paradigm for the treatment of ulcerative colitis has recently been presented: Treatment of the mucosa with lidocaine (2%) enemas for prolonged periods. This therapy was introduced based on the hypothesis that hyperreactive autonomic nerves may play a pathogenetic role in the disease. One hundred consecutive patients have now been treated and the results presented. Theproctitis patients all responded to the treatment, despite previous therapeutic failures in more than two-thirds of the cases. They were treated for 3–12 weeks, but 68% had a relapse (observation period 20 months). Of the 49 patients withproctosigmoiditis, two-thirds had chronic symptoms resistant to previous therapy. One of these patients did not respond to lidocaine, but developed fulminant total colitis. The other patient had therapeutic failure with lidocaine but responded well to subsequent cortisone enemas. The patients were treated until the subsets of T-lymphocytes (
and
) disappeared from the mucosa. This occurred in parallel with symptomatic relief and eventual healing in 83% of the patients after treatment for 6–34 weeks. Of all the patients with proctosigmoiditis, 42% presented with recurrent symptoms (observation period 16 months). Of the 17 patients withleft-sided colitis, all went primarily into remission within 2–4 months, but 23% had a relapse (observation period 13 months). The 6 patients withtotal colitis had symptomatic relief and improvement of histology when treated over 3–8 months. One patient had recurrence after 12 months. Treatment with a local anaesthetic in ulcerative colitis is a new approach to mucosal inflammation. The beneficial effects may be due to blockade of certain neural effects, such as epithelial proliferation and shedding and congestion of the mucosal vasculature, with actions on cells of the immune system.This work was supported by grants from the Swedish MRC (2207, 5520), the Assar Gabrielsson Foundation, and the Ulf Widengren Foundation. 相似文献
83.
84.
Davidson B Givant-Horwitz V Lazarovici P Risberg B Nesland JM Trope CG Schaefer E Reich R 《Clinical & experimental metastasis》2003,20(7):621-631
Activation or suppression of intracellular signaling via the mitogen-activated protein kinase (MAPK) family has been linked
to expression of matrix metalloproteinases (MMP) in experimental models, but this association has not been demonstrated in
clinical material. The objective of this study was to investigate the possible association between expression and activity
of MMP, expression of the MMP inducer EMMPRIN, and the expression (level) and phosphorylation status (activity) of the extracellular-regulated
kinase (ERK), c-Jun amino-terminal kinase (JNK) and high osmolarity glycerol response kinase (p38) in effusions from patients
diagnosed with serous ovarian carcinoma. MAPK level and activity were studied in 55 effusions using immunoblotting. MMP-1,
MMP-2, MMP-9 and EMMPRIN expression was studied using immunocytochemistry (ICC) and mRNA in situ hybridization (ISH). The
gelatinolytic activity of MMP-2 and MMP-9 was measured by zymography. ERK and phospho-ERK (p-ERK) were detected in 54/55 (98%)
and 50/55 (91%) specimens, respectively. JNK and p-JNK were detected in 53/55 (96%) and 38/55 (69%) specimens, respectively.
p38 was expressed in 54/55 (98%) specimens, and its phosphorylated form was found in 51/55 (92%). MMP-2 mRNA expression (P=0.048), protein expression (P=0.046) and gelatinolytic activity (P=0.039) correlated with ERK phosphorylative activity. MMP-2 activity also correlated with p38 activity (P=0.017). MMP-9 protein expression correlated with phosphorylation of p38 (P=0.046), but enzyme activity showed inverse relationship with both p-ERK (P=0.05) and p-p38 (P=0.033) expression. EMMPRIN expression correlated with MMP-1 (P<0.001), MMP-2 (P=0.042) and MMP-9 (P=0.029) expression, as well as with ERK activity (P=0.001). Our results present the first evidence of a possible link between MAPK signaling and MMP expression and activity
in vivo. These data may expand our understanding regarding the mechanisms by which MMP synthesis is regulated in effusions and possibly
affect treatment strategies for this form of malignancy.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
85.
86.
Fine-needle aspiration cytology (FNAC) plays a key role in the preoperative diagnosis of breast carcinoma but is less reliable in the diagnosis of in situ lesions. The objective of the present study was to investigate the cytological features of lobular carcinoma in situ (LCIS), regarding which little data is available to date. Cytological features of FNAC of the breast from 21 patients with histology-proven LCIS were described and compared with surgical specimens. Aspirates from 8/21 cases had cell groups diagnostic for or compatible with LCIS. Aspirates from an additional two cases demonstrated hypercellular, dissociated, and more pleomorphic tumor cells, which were originally diagnosed as invasive lobular carcinoma (ILC). The remaining 11 aspirates were diagnosed as benign or nondiagnostic. FNAC from the eight diagnostic specimens were characterized by loosely cohesive cell groups composed of uniform cells with occasional intracytoplasmic lumina, slightly irregular and eccentric nuclei. We conclude that the main difficulty in diagnosing LCIS by FNAC is sampling rather than recognition of the lesions. However, one should be aware of the cytological features of LCIS in order to reach a correct diagnosis. There are no reliable cytological criteria that help in differentiating pleomorphic and dissociated LCIS from ILC. 相似文献
87.
P A Bj?rkstrand 《Biological psychology》1990,30(1):35-50
The effects of conditioned stimulus (CS) pre-exposure and fear-relevance of the CS on human Pavlovian electrodermal conditioning were investigated. A differential delayed conditioning paradigm was used with a CS-unconditioned stimulus (US; shock) interval of 8 s. In Experiment 1, 64 subjects were randomized into four groups, two of which received fear-relevant stimuli and the other two fear-irrelevant stimuli. Half of the subjects were pre-exposed to the to-be-CSs and the other half to two not-to-be-CSs, with 15 exposure of each stimulus. During acquisition, subjects received 8 reinforced and 8 nonreinforced CS+ and CS- trials, and during the extinction phase 15 nonreinforced trials of each CS. Pre-exposure to the to-be-CSs retarded conditioning for the first and second interval anticipatory responses (FIRs and SIRs); that is, a latent inhibition effect was demonstrated, although the results for the FIR were inconclusive. The expected effects of fear-relevance were not revealed. Experiment 2 addressed the question whether the long pre-exposure period interfered with the frequently observed "preparedness effect" of higher resistance to extinction to fear-relevant stimuli. The design was similar to that of Experiment 1, but for half of the subjects the acquisition phase was initiated immediately after a short rest period, and for the other half acquisition started after an extended rest period, equal to the duration of the pre-exposure phase in Experiment 1. Twenty extinction trials of each CS were presented. A reliable difference in arousal in terms of spontaneous fluctuations was produced by the rest periods, but although differential conditioning was observed, no effect of fear-relevance was seen during extinction. 相似文献
88.
89.
Jonas Björk Jakob L Forberg Mattias Ohlsson Lars Edenbrandt Hans Öhlin Ulf Ekelund 《BMC medical informatics and decision making》2006,6(1):28-10
Background
Several models for prediction of acute coronary syndrome (ACS) among chest pain patients in the emergency department (ED) have been presented, but many models predict only the likelihood of acute myocardial infarction, or include a large number of variables, which make them less than optimal for implementation at a busy ED. We report here a simple statistical model for ACS prediction that could be used in routine care at a busy ED. 相似文献90.
The present study was a longitudinal study of age-related changes in performance of the 5-choice serial reaction time task, a test of visual attention. Following acquisition of the task, animals were tested on two occasions on their ability to perform the 5-choice task. In Test 1 (Young: 7 months; Aged: 13–14 months) no age-related effects on baseline performance were revealed. However, increasing the attentional load of the task revealed an impairment in choice accuracy by animals of the Aged group. In Test 2 (Young: 10–11 months; Aged 23–24 months), animals of the Aged group were significantly impaired on the baseline schedule of the task compared to the Young group. The deficit in accuracy on the task could be improved in the Aged animals by decreasing the attentional load. The results of the present study suggest a deficit in attentional function as a result of the aging process, markedly similar to that observed following lesions of the basalo-cortical cholinergic system. 相似文献