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51.
The binding of pertussis toxin and its B oligomer to lipid vesicles containing glycosphingolipids was studied. Both pertussis toxin and the B oligomer bound to lipid vesicles containing ganglioside GD1a. Binding of pertussis toxin to these vesicles decreased upon treatment of the vesicles with neuraminidase, suggesting that sialic acid residues are important for efficient binding of the toxin to GD1a. 相似文献
52.
HS Chen JW Pellegrini SK Aggarwal SZ Lei S Warach FE Jensen SA Lipton 《Canadian Metallurgical Quarterly》1992,12(11):4427-4436
Excessive activation of NMDA receptors is thought to mediate the calcium-dependent neurotoxicity associated with hypoxic-ischemic brain injury, trauma, epilepsy, and several neurodegenerative diseases. For this reason, various NMDA antagonists have been investigated for their therapeutic potential in these diseases, but heretofore none have proven to be both effective and safe. In the present study, memantine, an adamantane derivative similar to the antiviral drug amantadine, is shown to block the channels activated by NMDA receptor stimulation. From whole-cell and single-channel recording experiments, the mechanism of action of memantine is deduced to be open-channel block, similar to MK-801; however, unlike MK-801, memantine is well tolerated clinically. Compared to MK-801, memantine's safety may be related to its faster kinetics of action with rapid blocking and unblocking rates at low micromolar concentrations. Furthermore, at these levels memantine is an uncompetitive antagonist and should theoretically allow near-normal physiological NMDA activity throughout the brain even in the face of pathologically high focal concentrations of glutamate. These pharmacological properties confer upon memantine a therapeutic advantage against NMDA receptor-mediated neurotoxicity with few side effects compared with other organic NMDA open-channel blockers. Moreover, memantine is increasingly effective against escalating levels of glutamate, such as those observed during a stroke. Low micromolar concentrations of memantine, levels known to be tolerated by patients receiving the drug for the treatment of Parkinson's disease, prevent NMDA receptor-mediated neurotoxicity in cultures of rat cortical and retinal ganglion cell neurons; memantine also appears to be both safe and effective in a rat stroke model. These results suggest that memantine has considerable therapeutic potential for the myriad of clinical entities associated with NMDA receptor-mediated neurotoxicity. 相似文献
53.
Liver veno-occlusive disease is a severe toxic effect observed after bone marrow transplantation. Clinical manifestations are jaundice, painful liver enlargement, and fluid-sodium retention. Histologically there is non-thrombotic obliteration of the centro-lobular veins associated with centro-lobular necrosis. This severe complication of bone marrow transplantation occurs early and is caused by a toxic processing effect. Incidence is variable, 2 to 50% in reported series, depending on patients, type of marrow provessing and on diagnostic criteria (which hinders comparison between studies). According to most studies, veno-occlusive disease regresses spontaneously. Mortality, depending on the severity of the symptoms, varies from 20 to 50%. Pathogenesis remains under debate: the initial event would occur in the sinusoid endothelium creating a state of local hypercoagulability by release of tissue factors favoring deposit of coagulation factors, especially factor VIII, in the subendothelial region of the veinules. There is also a direct toxic effect on centro-lobular hepatocytes which is further aggravated by ischemia and venous stasis. use of heparin to prevent veno-occlusive disease was proposed by the Besan?on group in 1985 after they observed a low incidence (1 case in 65) in patients who were given low doses of heparin to maintain patent central catheters. The same team confirmed in 1992 the low incidence in a large retrospective series of 444 patients given either an autograft (3 cases in 253 patients, i.e. 1.2%), or an allograft (5 cases in 191 patients, i.e. 2.6%). Two single-center studies, one in Seattle and the other at the Saint-Antoine hospital in Paris, published in 1990 and 1991, did not show any difference in patients given heparin or not. Inversely, a randomized study published by Attal in 1992 including 161 patients showed a significant difference in the incidence of veno-occlusive disease between patients given heparin (2.5%) and those who were not given heparin (13.7%; p < 0.01). All these studies show that with low doses (100-150 U/kg) the risk is very very low. The mechanism of action of heparin would appear to be related to its protective effect on the endothelium rather than its hemostasis effect. The vascular protective effect of prostaglandin E1 suggests it might also be useful in preventing veno-occlusive disease. 相似文献
54.
OBJECTIVE: To investigate the understanding and expectations of defendants referred to Valkenberg Hospital for 30-day observation. DESIGN: Defendants referred for 30 days of psychiatric assessment were surveyed by means of a semi-structured interview within 3 days of admission. PARTICIPANTS: One hundred consecutive referrals from the Western, Northern and Eastern Cape were considered; 88 were eventually entered into the study. RESULTS: All defendants were generally ignorant of the reasons for referral, but had a good understanding of court procedure and wrongfulness. Mentally ill subjects differed only in their not being able to distinguish between a guilty/not guilty plea. Most did not have legal representation, did not personally request the assessment and denied guilt of the alleged offence. CONCLUSIONS: Mental illness affects triability but not necessarily criminal responsibility. Disturbingly, most defendants were without legal representation and were unaware of the purpose, implications and possible outcomes of psychiatric observation. It is imperative that the legislation governing these aspects be reviewed. 相似文献
55.
The application of a Silon pouch usually indicates a desperate if not impossible situation in which the abdominal contents cannot be returned to the abdominal cavity and therefore require some type of covering. Since 1968, we have had experience with 55 Silon pouches in infants and children. Almost all of these pouches were applied to newborns. There were 22 deaths in this series (40%), although 12 of these deaths were in the diaphragmatic hernia group and were almost all due to respiratory failure unrelated to the pouch itself. There were nine deaths in the gastroschisis and omphalocele group (28%) and in all these instances infection (especially Candida) was the underlying cause. While much debate exists as to how the Silon pouch should be handled after its application our series demonstrated that the longer it stayed in place the greater the chance of infection. Furthermore if broad spectrum antibiotics were used for a prolonged period of time, Candida overgrowth of the pouch followed by Candida sepsis and death were almost inevitable. 相似文献
56.
Traumatic rupture of the aorta. A five-year experience 总被引:1,自引:0,他引:1
SZ Turney S Attar R Ayella RA Cowley J McLaughlin 《Canadian Metallurgical Quarterly》1976,72(5):727-734
In the five-year period ending in October, 1975, 31 consecutive patients with traumatic rupture of the thoracic aorta underwent surgery at the University of Maryland Hospital or the Maryland Institute for Emergency Medicine. All cases were confirmed by preoperative aortogram. Rupture was confined to one or more sites in the descending thoracic aorta at or distal to the origin of the left subclavian artery. The age was a mean of 26 years. Operation was done within an average of 18 hours after injury. Significant nonthoracic injuries were present in every case. Six patients with positive findings on peritoneal lavage underwent exploratory laparotomy prior to thoracotomy because of shock. Surgical repair was done by use of left heart bypass in 2 cases (one death), a passive aorta-aorta shunt in 23 cases (5 deaths), and without shunt or bypass in 6 cases (no deaths). An end-to-end tubular Dacron graft was used to reconstruct the aorta in all but one patient. Over-all survival rate was 25 of 31 patients (81 per cent). Paraplegia developed in one patient and renal failure in 3 patients (2 deaths) in the aorta-aorta shunt group. Hypertension was present in 18 (72 per cent) of the survivors. Palsy of the left recurrent laryngeal nerve persisted in 8 (32 per cent) of the survivors. Two of the deaths were related to technical problems of the shunting procedure and 2 to intrapleural exsanguination before proximal aortic control could be achieved. Complications and blood loss were reduced in the group with no shunt. The series lends support to the rigorous aortographic search for ruptured thoracic aortas in trauma patients with widened mediastinum. Once experience has been gained with shunting techniques, tears of the descending thoracic aorta may be safely repaired without shunt if done expeditiously. 相似文献
57.
L Picariello ML Brandi L Formigli SZ Orlandini P Dolara G Caderni L Raimondi F Tonelli 《Canadian Metallurgical Quarterly》1998,360(1):105-112
A tadpole of bullfrog, Rana catesbeiana, is originally covered with the larval skin over its entire body. Drastic changes arise in both the epidermis and the subcutaneous connective tissue at an early developmental stage, producing the precursor of adult type skin (pre-adult skin). It was found that calcium is a useful probe to detect the region where the precursor formation has occurred because its deposition in the upper part of subcutaneous collagen bundles coincides with the appearance of the pre-adult skin. Whole-mount in situ staining of tadpoles with alizarin red S revealed the initiation site of the premetamorphic transformation of the larval skin into the adult precursor and its ensuing region-dependent expansion. The pre-adult skin first emerged at TK II to III (TK, Taylor and Kollros staging) t lateral sides of the body, which led us to postulate that 'the center for premetamorphic skin transformation' is formed at the specific site in this region. This center moved dorsally and then ventrally, then reached to the most proximal region of the tail, yielding a unique sequential conversion pattern by around TK V when the conversion was completed in the trunk. The present study also visualized the process of the hindlimb skin transformation. 相似文献
58.
Radiofrequency (RF) energy has many advantages in thermal tumor ablation protocols. With the recent development of open MRI systems, interventional MRI procedures, including thermal ablation, have become the focus of great research interest. However, the significant interference between RF generators and MR imagers has prevented simultaneous imaging and RF ablation and, until now, has limited the role of RF-based thermal therapy in interventional MRI. Here, a simple switching circuit designed with consideration of patient safety provides compatibility between open MRI systems and RF thermal lesion generators. The experimental results show that the switching circuit allows imaging during RF ablation and opens new opportunity for MR-guided thermal therapy. 相似文献
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60.
K Cao M Mizokami E Orito X Ding R Ueda G Chen SZ Yu S Tokudome 《Canadian Metallurgical Quarterly》1998,13(12):1241-1248
The latest meeting of the AAMC's Forum on the Future of Academic Medicine, on April 29, 1998, opened with a talk by Francis S. Collins, MD, PhD, director of the National Human Genome Research Institute, who reviewed the significant progress that the Human Genome Project (HGP) has made and speculated on how genetic discoveries and technologies would transform health-related research and ultimately the practice of medicine. The HGP's findings will offer clear improvements in diagnosis and prevention, and eventually in treatments, and the relationship between the academic medical center and the pharmaceutical industry will change--but remain good--as that industry applies the findings of the HGP. He stressed the need for the public and health care providers to develop a greater understanding of genetic issues, and urged changes in medical education to accomplish this. Forum members and Dr. Collins discussed the ethics and economics in patient care resulting from genetic research; forum members also asked whether academic medical centers could profit from genetic research findings. The second speaker was John Eisenberg, MD, administrator of the Agency for Health Care Policy and Research, which fosters health care research and disseminates to clinicians and others the findings of such research. Among other topics, Dr. Eisenberg described the new emphasis on health care outcomes and quality and described how his agency promotes research in these areas. Forum members asked who would pay for the information systems needed to communicate the findings of health services research and also noted that there is an expanding definition of health that places new pressures on already stressed academic medical centers, their missions, and their curricula, which must change. Michael Whitcomb, MD, of the AAMC, noted that the view that medical schools can't change their curricula has been proved wrong, and that 24 medical schools are working with the AAMC's Medical Schools Objectives Project on curricular reform. The forum closed with discussion of a few broader issues affecting academic medical centers. 相似文献