Background: Recent reports indicate increased incidence of Clostridium botulinum infections, particularly among drug abusers and tissue allograft recipients. Botulinum toxin also has potential application in biochemical warfare. The neurotoxin-induced paralysis often requires mechanical ventilation with and without muscle relaxants. The authors investigated the long-term effects of botulinum toxin on muscle function, expression of nicotinic acetylcholine receptors (nAChRs), and their interaction with muscle relaxant, atracurium.
Methods: Rats (n = 30) were injected with varying doses (0.625, 2.5, and 10 U) of botulinum toxin into the tibialis muscle. Control animals (n = 9) received an equivalent volume of saline. At 128 days after injection, neuromuscular function, pharmacodynamics of atracurium, and nAChRs were evaluated.
Results: Nerve-evoked tensions, including tetanic tension and muscle mass, were decreased on the toxin-injected side in a dose-dependent manner relative to saline-injected controls as well as the contralateral side. Specific muscle tension and specific tetanic muscle tension (tensions/muscle mass) were not reduced. The ED10 of atracurium was reduced, the ED50 was unchanged, and the ED90 was increased in the highest (10-U) dose of toxin group. The atracurium plasma concentration to maintain a steady state 50% paralysis was significantly reduced in the 10-U toxin group. The nAChR concentrations in the tibialis muscle were significantly increased in a dose-dependent manner in all experimental groups. 相似文献
A new series of N-(substituted)benzyl-1,8-naphthalimides 4, structurally related to the previously reported thymidylate synthase (TS) inhibitor naphthaleins 3, were synthesized and compounds tested for their inhibition of several species of TS. Moreover, their in vitro cytotoxicity together with antimycotic and antibacterial properties were assayed. While no activity was detected in the antibacterial tests, the m-nitro (4ae) and the p-nitro (4af) derivatives were found able to partially inhibit TS at low micromolar concentrations. Introduction of nitro or (substituted)-amino groups in position 4 of the naphthalic ring always led to less active compounds. 相似文献
Acute mesenteric ischemia, a frequently lethal disease, requires prompt diagnosis and intervention for favorable clinical
outcomes. This goal remains elusive due, in part, to lack of a noninvasive and accurate imaging study. Traditional angiography
is the diagnostic gold standard but is invasive and costly. Computed tomography (CT) is readily available and noninvasive
but has shown variable success in diagnosing this disease. The faster scanning time of multidetector row CT (M.D.CT) greatly
facilitates the use of CT angiography (CTA) in the clinical setting. We sought to determine whether M.D.CT-CTA could accurately
demonstrate vascular anatomy and capture the earliest stages of mesenteric ischemia in a porcine model. Pigs underwent embolization
of branches of the superior mesenteric artery, then imaging by M.D.CT-CTA with three-dimensional reconstruction protocols.
After scanning, diseased bowel segments were surgically resected and pathologically examined. Multidetector row CT and CT
angiography reliably defined normal and occluded mesenteric vessels in the pig. It detected early changes of ischemia including
poor arterial enhancement and venous dilatation, which were seen in all ischemic animals. The radiographic findingsd—compared
with pathologic diagnosesd—predicted ischemia, with a positive predictive value of 92%. These results indicate that M.D.CT-CTA
holds great promise for the early detection necessary for successful treatment of acute mesenteric ischemia.
Presented at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–18,
2005 (oral presentation).
Supported by the Karin Grunebaum Research Fellowship, Harvard Medical School (D.E.R.), the German Research Fellowship, German
Research Foundation STR 690/1-1 (O.S.), and the Phillip H. Meyers Grant from the Society of Gastrointestinal Radiologists
(S.P.T.). 相似文献
We report an instance of critical ovarian hyperstimulation syndrome in a
highly responsive in-vitro fertilization patient despite the preventive
measure of a 4 day 'coast' interval during which no gonadotrophins were
administered while gonadotrophin-releasing hormone agonist therapy
continued until serum oestradiol concentrations fell below 3000 pg/ml.
相似文献
INTRODUCTION: Core biopsy of the breast has become the method of choice for tissue diagnosis of screen detected microcalcifications and some mass lesions in many breast assessment centres. Biopsy results are not available until the following day. Imprint cytology of fresh breast core samples allows same-day reporting and patient counselling. AIM: To determine the accuracy of core imprint cytology when compared with core biopsy diagnosis when used in a breast assessment centre setting. METHODS: Core imprints (CI) were prepared and reported on all fresh core biopsies (CB) performed at the Sir Charles Gairdner Hospital Breast Centre from May to December 2000. Fresh core samples were placed on a glass microscope slide. Core radiographs were taken for microcalcification lesions (MC). A laboratory technician gently and quickly rolled the cores on the slide with fine forceps. The cores were fixed in formalin, processed and reported next day. The imprint slide was air dried and stained with DiffQuik. CI were reported using four categories: Insufficient, Benign, Indeterminate and Malignant. Counselling and planning for management were possible on the same day in women with malignant diagnoses. Clinicians were advised not to discuss negative or indeterminate CI results with women and to defer to the final CB report. RESULTS: Cores were performed on 381 lesions. There were 83 carcinomas (38 in MC and 45 in masses) and 56 were called malignant on CI (absolute sensitivity 67.5%; 78.9% for MC and 57.8% for masses). 3 malignancies on CB were negative on CI giving a false negative rate of 3.6%. There were no false positive diagnoses. The predictive value of a benign diagnosis was 95.3%. There were no adverse effects in the histology of CB. CONCLUSION: CI was an accurate method of providing an immediate diagnosis of malignancy in two thirds of malignancies confirmed on CB. 相似文献
Summary An immunoconjugate composed of natural interferon (nIFN) bound in a noncleavable fashion to a monoclonal antibody (MoAb) recognizing a breast epithelial membrane mucin (Mc5) was used to treat xenografts of a human mammary carcinoma cell line (MCF-7) growing in nude mice. The immunoconjugate (nIFN/Mc5) was administered as 20 intralesional (i.l.) injections to 1 of 2 xenografts in each animal. It was found that nIFN/Mc5 produced a significant enhancement of the growth inhibitory actions of nIFN on the injected tumors. Further enhancement was obtained when nIFN or nIFN together with Mc5 (at a dose 10 times larger than that present in nIFN/Mc5) were added to the immunoconjugate. Biodistribution experiments showed that the uptake of125I-nIFN/Mc5 by the tumors was greater and its elimination slower than for125I-nIFN alone or conjugated to irrelevant mouse IgG1. In addition, the immunoconjugate up-regulated the antigenic expression of a breast epithelial membrane mucin by the carcinoma cells, an up-regulation which was not significantly different from that produced by nIFN alone. The contralateral noninjected tumors exposed to systemic levels of the immunoconjugate showed an enhancement of antitumor effects, but to a lesser extent than the injected tumors. These findings suggest that the enhancement of the growth inhibitory action of the immunoconjugate was related to the specific binding of Mc5 which targeted the IFN to the carcinoma cells and impeded its elimination. It is likely that the targeting was favored by the IFN-mediated up-regulation of antigenic expression by the carcinoma cells, thereby producing a cascade of interrelated effects. The results of this study point out the feasibility and potential usefulness of IFN treatment by means of immunoconjugates as well as the worth of pursuing and improving this form of therapy. 相似文献